Aspirins and Antibiotics Curse or Cure – Study

  Aspirins and Antibiotics Curse or Cure – Study

Thanks to Dr. Jochen Schacht, and Dr. Su-Hua Sha. Their test results including ‘aspirin and antibiotics’ appears in the April 27 issue of The New England Journal of Medicine.

April 26, 2006

Aspirin shows promise in combating a common, antibiotic-induced hearing loss

University of Michigan, Chinese hospital find high success rate at preserving hearing when aspirin is paired with widely used antibiotic

ANN ARBOR, MI –Around the world, inexpensive antibiotics known as aminoglycosides have been used for the past 60 years in the battles against acute infections and tuberculosis, as antibacterial prophylaxis in cystic fibrosis patients, and other conditions. But for all of the good they do, the drugs also have been widely linked to irreversible hearing loss.

Jochen Schacht, Ph.DNow, researchers at the University of Michigan’s Kresge Hearing Research Institute and their Chinese colleagues, working under the leadership of Jochen Schacht, Ph.D., and Su-Hua Sha, M.D., have found that the hearing loss can be prevented in many people with the use of another inexpensive, widely available medication: aspirin. The results appear in the April 27 issue of the New England Journal of Medicine.

The researchers studied 195 patients in China who received 80 to 160 milligrams of gentamicin (a type of aminoglycoside) intravenously twice daily, typically for five to seven days. Of those, 89 patients were given aspirin along with the antibiotic, and 106 were given placebos along with the antibiotic. The results were dramatic: The incidence of hearing loss in the group that was given placebos was 13 percent, while in the aspirin group it was just 3 percent, or 75 percent lower.

“We would like to see the word get around to the medical community around the world that you can take some precautions to minimize the risk to your patients. Aspirin is available everywhere, and it’s cheap,” says senior author Schacht, professor of biological chemistry in otolaryngology at the University of Michigan Medical School and director of the U-M Health System’s Kresge Hearing Research Institute. Gentamicin is not commonly used in the United States.

He notes that this research builds on earlier U-M studies that showed promise in combating drug-induced hearing loss in the laboratory. “Previously we found that such a treatment works well in mice, but I am very excited that this worked so well in humans,” says Schacht. “Translating animal studies into clinical practice is not an easy thing to do. We were fortunate that our extrapolation from mice to men and women worked in the first trial.”

Su-Hua Sha, M.D.The research is exciting, says lead author Sha, because hearing loss caused by these antibiotics is so prevalent. The incidence of aminoglycoside-induced hearing loss averages 8 percent but the numbers may be higher in developing countries, she notes, where aminoglycosides are frequently the only affordable antibiotics and are sold over the counter. No therapy currently exists to prevent ototoxicity.

This research began in 1999 with a collaboration with Chinese hospitals. Working with Schacht, Sha – associate laboratory director of U-M’s Kresge Hearing Research Institute’s Biochemistry Laboratory – got in touch with her colleagues in China. The two traveled to China and presented their ideas, and ultimately began a partnership with the Fourth Military Medical University in Xi’an, China. The third author on the paper, Jian-Hua Qiu, M.D., represents the colleagues of the Fourth Military Medical University.

After receiving approvals from institutional review boards at U-M and the Fourth Military Medical University, the otolaryngology department in Xi’an conducted the prospective, randomized, double-blind trial at Xijing Hospital and Airforce Chengdu Hospital from 1999 to 2003. All of the participants were ages 18 to 65, and were inpatients who were scheduled for treatment with gentamicin. Hearing damage, or ototoxicity, was defined as a shift from a person’s baseline hearing by at least 15 decibels at both the 6 and 8 kHz frequencies, which are the first affected by the drugs. The effectiveness of the gentamicin as an antibiotic did not lessen when it was paired with aspirin.

Schacht notes that even though gentamicin has been linked widely with hearing loss, and its use has been declining in industrial countries, it is not practical to think that it will be replaced in the near future by other antibiotics because it has specific applications and is so inexpensive and available, especially in poor countries. While aspirin shows promise, and he hopes that health care providers pair it with gentamicin, he also notes it is not yet the perfect solution because of the potential side effects of aspirin, including gastric bleeding. And he notes that this is an off-label use of aspirin, which may inhibit some practitioners from giving it to patients in such instances.

He hopes that further studies will lead to the development of new and safer antibiotics, or another drug that can be paired with gentamicin that has fewer side effects than aspirin. He and Sha are exploring partnerships with other countries to conduct future research.

Funding for the research came from George and Christine Strumbos and the Kent and Carol Landsberg Foundation.

Citation: New England Journal of Medicine, Volume 354, Issue 17: April 27, 2006.

Written by Katie Gazella

Additional Hearing Loss Studies:

ARO Abstracts 1 Volume 25, 2002
Hereditary Hearing Impairment
*James F. Battey
, NIDCD, NIH, Bethesda, MD 20813
There has never been a greater opportunity for research to make an
immediate impact on human diseases and disorders than exists at this
time. Remarkable progress has been made in determining the structure
of the human genome, with thousands of useful markers mapped and
about 50% of the sequence determined. Public databases contain a
partial sequence from over 90% of all genes that are expressed. This
infrastructure provides the fuel for discovering the genes that determine
susceptibility to communication disorders such as hereditary hearing
It is estimated that one child in a thousand is born with hearing
impairment that compromises the development of normal language
skills. In the majority of cases, the cause of hearing impairment is
mutations in genes which result in hearing impairment in the absence of
any other clinical findings (nonsyndromic autosomal dominant,
recessive, or X-linked hereditary hearing impairment). Within the last
six years, scientists have determined the location in the genome of over
seventy genes that cause nonsyndromic hereditary hearing impairment.
Over twenty of these genes have been cloned. These genes encode
proteins with varied functions, including unconventional myosins
(intracellular motor molecules), transcription factors (gene regulatory
proteins), cadherins and claudins that form specialized junctions
between cells, and intra- and inter-cellular signaling molecules. These
breakthroughs provide the tools for precise determination of the
etiology of hereditary hearing impairment, leading to early intervention
that will optimize development of language skills, as well as
intervention strategies in cases where the hearing impairment is
progressive. Understanding the genes whose mutation results in
hereditary hearing impairment will provide a fundamental new
understanding of the molecular and cellular functions that are essential
for normal auditory function.
Stem Cells and Precursor Cells for Sensorineural
Transplantation in the Auditory System.
*Allen F. Ryan
, Kwang Pak, Jill DeFratis, Thecla Bennett, Lina M
Mullen, Otolaryngology, UCSD, VAMC, 9500 Gilman Drive,
0666, La Jolla, CA 92093-0666
The loss of hair cells and/or primary sensory neurons is the most
common cause of sensorineural hearing loss and peripheral vestibular
disorders. Once lost, neither cell type regenerates in mammals. The
possibility of transplantation to replace lost cells has received relatively
little attention in the inner ear. However, there have been recent
advances in our understanding of how hair cells and inner ear neurons
arise and differentiate. In addition, stem cells of various origins are
increasingly available. This suggests that it may eventually be possible
to engineer stem cells into either sensory cells or sensory neurons.
These cells might be derived from the tissues of a patient, allowing
autologous transplants. To assess the potential for inner ear
transplantation, we have explored the feasibility of transplanting stem
cells, committed but undifferentiated precursor cells, and partially or
fully differentiated cells in the inner ear.
Using in vitro models we have found that immature hair cells can be
successfully transplanted into a previously damaged inner ear sensory
epithelium. They can integrate into the sensory epithelium, and form
new stereociliary bundles. Neither uncommitted stem cells from the
sensory epithelium of the developing inner ear, nor neural stem cells
derived from the central nervous system showed similar integration.
Fully differentiated sensory cells derived from the adult inner ear also
were not successfully transplanted. Immature sensory cells transplanted
into the adult cochlea in vivo survived for weeks, but did not display
integration into the organ of Corti.
Supported by NIH/NIDCD grant DC00139, and by the Medical
Research Service of the VA.
Plasticity and Refinement of Projections in the Auditory
Nervous System
*Patricia A. Leake
, Russell L. Snyder
Epstein Laboratory,
University of California, U 490, Department of Otolaryngology,
San Francisco, CA 94143-0526,
Otolaryngology, University of
California, San Francisco, CA
In most mammals the auditory system is so immature at birth that
neonates are deaf. This provides a valuable opportunity to study
molecular and activity-dependent mechanisms contributing to formation
of precise connections, emergence of specific functional capacities and
plasticity. We have studied the development of auditory nerve (AN)
projections to the cochlear nucleus (CN) by labeling small sectors of the
cochlear spiral ganglion representing a narrow band of frequencies in
kittens. Results show that projections from the basal cochlea exhibit
clear tonotopic organization before birth, in kittens studied after C-
section at 60-64 days gestation, prior to emergence of spontaneous
activity in the AN and many days before the onset of functional hearing.
However, our data also demonstrate that significant refinement of CN
projections occurs during early postnatal maturation. Topographic
restriction of fibers into frequency band laminae is less precise in all 3
CN subdivisions in perinatal kittens than in adult cats. Projections to
the AVCN, PVCN, and DCN are 53%, 36% and 32% broader,
respectively, in neonates than in adults when normalized for CN size.
Preliminary data suggest that the precise organization of these
projections is stable even when AN nerve activity is greatly reduced or
abolished neonatally by ototoxic drug deafening. On the other hand,
marked alterations in projections to the inferior colliculus (IC) occur
after neonatal unilateral cochlear ablation, and stimulation by a cochlear
implant in neonatally deafened animals can induce significant
functional plasticity in the IC. Future studies will determine whether
neuronal activity is essential for refinement of the AN projections to the
CN and the extent to which these projections may be modified by
aberrant input during the subsequent critical period.
(Supported by NIDCD Grant RO1 DC00160.)
Experience and Auditory Brainstem Development:
Signals, Cellular Events and Critical Periods
*Edwin W Rubel
, Virginia Merrill Bloedel, Otolaryngology-HNS, VMB
Hearing Res Ctr, University of Washington, Box 357923, Seattle,
WA 98195-7923, Hearing Research Center and Department of
Otolaryngology-Head and Neck Surgery, University of
Washington, Seattle, WA
Since the classical experiments of Hubel and Wiesel, a large variety of
studies have shown that manipulations of sensory experience have
profound influences on the development of sensory encoding pathways
of the central nervous system. Yet little is known about the cellular
mechanisms whereby changes in sensory system function influence the
structure or integrity of CNS elements. We have used the brainstem
auditory pathways of birds and mammals to investigate the early
cellular events underlying deprivation- and deafferentation-induced
changes in the structure and integrity of neurons and glial cells. I will
discuss a series of in vivo and in vitro experiments which address three
issues related to activity-regulated development and maintenance of
cochlear nucleus neurons. What is the nature of the intercellular signals
regulating structural integrity of postsynaptic neurons? What are some
of the intracellular cascades of events underlying deprivation-induced
changes in neuronal integrity? What biological mechanisms may
underlie developmental differences in responses to peripheral
manipulations (critical periods)?

ARO Abstracts 4 Volume 25, 2002
substances, closely correlating with development of the EP. It is of
interest that certain components of the Wingless/Wnt signaling pathway
are colocalized in the EGJS over the same developmental time course,
in particular
-catenin and the adenomatous polyposis coli protein,
APC, and two other proteins possibly involved in regulating
activity, presenilin 1 and
-catenin (R. Killick, unpubl. observ.). Certain
connexins are known Wnt target genes, and Wnt signaling can also
modulate gap junction permeability in a transcriptionally independent
manner. It is conceivable that the Wingless/Wnt pathway of the EGJS
also interacts with the SCF
(Supported by NIH-NIDCD grant DC01414).
Multiple Claudins are expressed in Outer Hair Cell ñ
Supporting Cell Tight Junctions where they form a Unique
Permeability Barrier and Adhesive Complex
Lanier Lopez, Celine Pompeia, Caroline Davies, Ricardo B Azevedo,
Inna A Belyantseva, Agnieszka Rzadzinska, Fabio Nunes,
Bechara Kachar
, Section on Structural Cell Biology,
NIDCD/NIH, Bldg 36, Room 5D15, Bethesda, MD 20892-4163
At the level of the reticular lamina, the apical surfaces of outer hair cells
and supporting Deitersí cells are structurally interlocked and sealed by a
distinct tight junctional complex. Claudins, a large family of
transmembrane proteins, are the primary seal-forming elements of the
extracellular space in tight junctions and presumed to be expressed in a
cell and tissue specific manner. In a PCR screening of various mouse
tissues, we found that multiple claudin species are expressed in the
organ of Corti. Using an immunofluorescence assay with custom made
antibodies to each of the known mammalian claudins, we observed that
several claudins including 1,2, 3, 6, 9 and 14 are represented at the tight
junction around the outer hair cells (OHC). A comparison of the
intensity of the labeling signal indicates that claudin 9 is clearly the
predominant isoform. We have further studied the structure and
molecular content of this junctional complex using freeze-etching and
immunogold labeling electron microscopy. Although adherens
junctions and the adherens junction proteins E-cadherin,
- and
catenin are present in Deitersí cell-Deitersí cell junctions, they are not
found in the OHCs-Deitersí cell junctions. However, the adherens
junction proteins
-catenin and p120 were found not only between
Deitersí cells but also in OHC-Deitersí cell junctions. Our observations
lead us to conclude that the OHC-Deitersí cell junction is an enhanced,
hybrid tight junction that functions as both permeability barrier and
adhesion complex. This unique tight junction may derive its effective
permeability and adhesive capacity from interactions between multiple
claudin isoforms and the components of the
-catenin and p120
complex. Such unique molecular composition may account for this tight
junctionís ability to maintain its integrity despite the vigorous motion
generated in the cochlear partition during sound transduction and OHC
Connexins 31 and 45 are expressed on the mouse inner
*Joe C. Adams
, ENT Department, Massachusetts Eye & Ear Infirmary,
243 Charles Street, Boston, MA 02114
The prevalence of deafness associated with mutations in genes that
encode gap junction proteins, connexins, attests to critical roles played
by gap junctions in the inner ear. Usually more than one form of
connexin is present within a given connexon (gap junction) and it is
thought that functional properties of given connexons are conferred by
their connexin composition. Previous work has indicated the presence
of connexins 26 and 30 within connexons joining all cochlear cells that
are joined by gap junctions, although it is not established that all
cochlear gap junctions contain these connexins. Hearing loss has been
associated with mutations in connexin 26 and 30 genes. Connexin 43
has recently been associated with sensorineural hearing loss but the
cells that express this connexin are not yet well characterized. Hearing
loss has also been associated with connexin 31 mutations in humans and
immunostaining of rat and mouse ears indicate that its distribution is
limited to type II fibrocytes and cells of the spiral limbus. However, the
presence of connexin 31 in the mouse inner ear has been questioned by
Plum et al. This report reports the presence of mRNA encoding
connexins 31 and 45 in the mouse cochlea. The presence of connexin 45
within the cochlea was indicated by positive findings using a restriction
fragment differential display assay. This finding prompted acquisition
of primers designed specifically for connexins 31 and 45 and
performing RT-PCR reactions on mouse inner ear samples. Results with
the specific primers confirmed the expression of both connexin genes
within the mouse cochlea. The results question the supposition that
mouse and human cochleas differ with regard to connexin content and
indicate that further study of connexin 45 within the ear should add to
the growing body of knowledge concerning the connexin family as
critical cochlear components.
Supported by NIDCD grant DC 03929.
Cation Absorption By Reissnerís Membrane Via
Epithelial Sodium Channels (ENaC)
*Jun-Ho Lee
, Daniel C. Marcus, Anatomy & Physiology, Kansas State
University, 1600 Denison, Manhattan, Kansas 66506
The epithelial cells of Reissnerís membrane (RM) form most of the
boundary of the cochlear duct. Little is known about the contribution of
RM to the ionic homeostasis of endolymph. Several lines of evidence
suggested a role in both Cl and cation transport. We have isolated RM
and looked for evidence of electrogenic transepithelial ion transport
with the vibrating probe. The lateral wall was dissected from the apical
turn of adult gerbil cochleae, the stria vascularis removed and the
attached portion of RM folded over the suprastrial portion of the spiral
ligament and perfused at 37∞C. The tip of the probe was positioned
about 20 μm from the apical surface of RM and a current (Isc) was
recorded flowing in the apical to basolateral direction. Isc was reduced
by blockers of the epithelial sodium channel (ENaC). Benzamil
inhibited Isc with an IC50 of 140 nM, amiloride with an IC50 of 1.2
μM, and EIPA with an IC50 of 70 μM. This sequence of potency is
consistent with dependence of the current on ENaC and not on a Na/H
exchanger. Isc depended on activity of the Na-pump since Isc was
inhibited by ouabain. Isc was not due to other cells in the preparation,
since removal of RM resulted in no detectable currents from the same
portion of the spiral ligament. Previous reports by several groups
suggested that RM contained a cAMP-dependent Cl pathway.
Stimulation of this pathway by 10 μM forskolin in this preparation
slowly decreased Isc but the underlying mechanism has not yet been
identified. These results show for the first time that Reissnerís
membrane is capable of transporting Na out of cochlear endolymph via
ENaC and may also provide a parasensory pathway for K efflux if the
permeability of ENaC to this ion is sufficiently high.
Supported by NIH NIDCD grant R01-DC212.
Secretion in Strial Marginal Cells and Vestibular
Dark Cells is Controlled by the Extracellular Osmolarity
*Philine Wangemann
, Elias Q. Scherer, Jun-Ho Lee, Daniel C Marcus,
Anatomy & Physiology, Kansas State University, 1600 Denison
Ave., Manhattan, Kansas 66506
The osmolarity of the basolateral fluid has been shown to control the
rate of K
secretion and the activity of the apical KCNE1/KCNQ1 K
channel in vestibular dark cells (VDC) (Wangemann et al., 1995). The
aim of the present study was to determine whether osmotic challenges
control the rate of K
secretion in strial marginal cells (SMC) of stria
vascularis. Morphometric measurements were made with
videomicroscopy and K+ secretion was measured with the vibrating
probe as current density in the vicinity of the apical membrane.
Osmolarity changes were introduced by addition and removal of
mannitol. A 10% osmotic challenge caused in stria vascularis within
60s no changes in cell width and nearly a 10% change in tissue height.
In VDC no changes in cell width and a 3% change in cell height were

ARO Abstracts 5 Volume 25, 2002
observed. The 10% hypoosmotic challenge induced in SMC and VDC
a transient 50 and 42% increase in the current density near the apical
membrane, respectively. Conversely, the 10% hyperosmotic challenge
caused a transient 30 or 44% decrease in the current density,
respectively. In conclusion, the data demonstrate that VDC regulate
their volume. It remained unclear, however, whether SMC of stria
vascularis regulated their cell volume. Both cell types, however,
responded to osmotic challenges with a change in the rate of K
secretion that would be consistent with cell volume regulation. The
similarity in the responses suggests an involvement of the apical
channel in both cell types. Interestingly, the
osmotically induced changes in the transepithelial current exceeded
those estimated to be necessary for cell volume regulation.
Supported by NIH-RO1-DC01098
Protein Identification, Glycosylation and
Immunolocalization of
-Adrenergic Receptors in the
Cochlea and the Vestibular Labyrinth
*Claudius Fauser
, Philine Wangemann, Anatomy & Physiology,
Kansas State University, 1600 Denison Ave., Manhattan, Kansas
-adrenergic receptors (
-AR) have been found to stimulate K
secretion in strial marginal cells and vestibular dark cells (Wangemann
et al., 1999, 2000). The aim of the present study was to identify
protein, to determine the glycosylation status, and to localize
-AR in
inner ear tissues. Crude membrane preparations of gerbil inner ear
(lateral wall, modiolus and vestibular labyrinth) and kidney were
prepared for Western blotting. Samples were digested with N-
glycosidases, Endo H and PNGase F, and separated by SDS-PAGE.
Proteins were detected by a rabbit polyclonal
receptor antibody (AB),
and visualized as chemiluminescence with an HRP-conjugated anti-
rabbit AB. Cryosections were prepared from decalcified, zinc-formalin
perfused, gerbil temporal bones.
-AR were localized by the rabbit
polyclonal AB and visualized with an Alexa-488-conjugated anti-rabbit
AB. Specificity of labeling was evaluated by preabsorption of primary
ABs with the peptide the AB was raised against. Western
immunoblotting of crude kidney membrane preparations revealed
specific bands at 145, 90, and 63 kDa. Digestion with PNGase F
(deglycosylating complex and high-mannose oligos
accharides) shifted
the 145 kDa band to 120 kDa and the 90 kDa band to 75 kDa.
Digestion with Endo H (deglycosylating only high-mannose
oligosaccharides) shifted only the
145 kDa band to a 120 kDa band.
Similar (not identical) bands and shifts were found for inner ear tissues.
Confocal microscopy revealed specific staining for
-AR in strial
marginal cells, spiral ganglia cells, inner and outer hair cells, Reissnerís
membrane and vestibular dark cells. These data demonstrate that
occur as high-mannose and complex-glycosylated proteins and that they
are localized in sensory and non-sensory cells of the inner ear.
Supported by NIH-ROI-DC01098
-adrenergic receptors stimulate chloride secretion in
semicircular canal duct epithelium
Pierre G. Milhaud
, *
Daniel C Marcus
, Jun-Ho Lee
, Michael Herzog
Philine Wangemann
Vestibular Neurobiology, Montpellier
University, Montpellier, F 34095 France,
Anatomy &
Physiology, Kansas State University, 1600 Denison Ave.,
Manhattan, KS 66506
The semicircular canal epithelium (SCE) is known to contribute to
endolymph homeostasis (Milhaud et al., 1999). The aim of the present
study was to investigate whether the transepithelial current I
is a) due
to net anion secretion or cation absorption, b) under hormonal control
and c) representative of the function of native neonatal and adult
epithelium. Cultured neonatal rat SCE mounted in an Ussing chamber
was used for I
and ionic flux measurements. Native neonatal rat and
adult gerbil SCE were used for I
measurements with the vibrating
probe and for cAMP measurements using a colorimetric immunoassay.
In cultured neonatal rat SCE I
was carried by a net
Isoproterenol (ISO, 10 μM) stimulated I
and net
flux but had no
effect on
fluxes. ISO and norepinephrine stimulated I
with an EC
of 8.0 nM and 15 nM, respectively. Adenosine, histamine
and vasopressin had no effect on I
. Forskolin stimulated I
, however,
had no further effect after full stimulation with ISO or norepinephrine.
The effect of ISO on I
was inhibited by the antagonists ICI118551 and
CGP20712A with K
values of 0.2 and >10 μM. Similar K
were obtained by measuring ISO-induced cAMP accumulation in native
neonatal rat SCE. In native neonatal rat and adult gerbil SCE I
stimulated by forskolin and ISO. In conclusion, our data validate the
use of cultured neonatal rat SCE as a model for native neonatal rat and
native adult gerbil SCE. The data demonstrate that the SCE contributes
to endolymph homeostasis by secreting Cl
and that Cl
secretion is
under hormonal control via
-adrenergic receptors.
Supported by INSERM and NIH-RO1-DC00212.
Endothelin-1 Induced Ca
-Sensitization of the Spiral
Modiolar Artery is Mediated by Rho-Kinase and Reversed
*Elias Q. Scherer
, Michael Herzog, Philine Wangemann, Anatomy &
Physiology, Kansas State University, 1600 Denison Ave.,
Manhattan, KS 66506
The spiral modiolar artery (SMA) contains ET
and CGRP receptors
(Scherer et al., 2001, Herzog et al. 2001). Endothelin-1 (ET1) induces a
transient increase in the cytosolic Ca
concentration ([Ca
]i) and a
long-lasting constriction suggesting an increase in the Ca
of the myofilaments. The aim of the present study was to determine
whether the ET1-induced Ca
-sensitization is mediated by Rho-kinase
and reversed by the vasodilator CGRP. A further aim was to visualize
the actin cytoskeleton.
The Ca
-sensitivity of the myofilaments was evaluated by a correlation
between [Ca
]i increases and associated vasoconstrictions. [Ca
]i and
the vascular diameter were measured with fluo4-microfluorometry and
videomicroscopy. Changes in [Ca
]i were induced by changes in the
extracellular Ca
concentration ([Ca
) from 0 to 1, 3 and 10 mM.
Increases in [Ca
caused increases in [Ca
]i and constrictions. ET1
(0.1 nM) had no significant effect on [Ca
-induced changes in [Ca
but caused a significant increase in the magnitude of the associated
constrictions. This observation suggests that ET1 increased the Ca
sensitivity of the myofilaments. This ET1-induced Ca
was prevented by the Rho-kinase antagonist 1
M Y-27632 (n=6) and
by 10 nM CGRP (n=6). The actin cytoskeleton was visualized by
Alexa-488-conjugated phalloidin in fixed and permeabilized vessels.
Confocal microscopy revealed that smooth muscle cells of the SMA
contain a single layer of thick actin bundles.
In summary, these data demonstrate that ET1 induces a Ca
sensitization of the myofilaments through activation of Rho-kinase and
that CGRP causes a desensitization of the myofilaments.
Supported by NIH RO1-DC04280
Ventral approach to inner ear in rat can preserve
cochlear function
Jianxin Qiu
, Goran Laurell
, Erik G. Borg
, *
Maoli Duan
Karolinska Instititutet, Stockholm 171 76 Sweden,
Neuroscience, Karolinska Institutet, Stockholm, Sweden,
Medical Center Hospital, Ahlsen Research Institute, 701 85
Orebro, Sweden
Investigation of cochlear function is often hindered since the
mammalian inner ear is difficult to reach wit
hout cochlea functional
change, particularly in the rat and mouse. The cochlea of the rat and
mouse is much smaller than that of guinea pig and rabbit. However, the
rat and mouse offer more experimental advantages than other species
such as guinea pig and rabbit since their genome is well characterised
and in addition, there is significant homology between rodents and

ARO Abstracts 6 Volume 25, 2002
human genome especially mouse. The goal of the present study was to
develop a new surgical method to
access rat cochlea. A ventral
approach through the neck to access the
ace of the tympanic
bulla was performed. 10 rats were investigated in the study and a small
hole was made in the cochlea at the scala tympani.. Auditory brainstem
response (ABR) was measured from 4 kHz to 40 kHz at pre and post-
surgery. We found that ABR thresholds were not statistically different
between pre and post-surgery. Thus the ventral approach to the rat
cochlea is safe and advantageous since it gives the surgeon more direct
view of the cochlea and round window, and in particular it avoids injury
of the stapedial artery as compared to post-auricular approach to the
inner ear. Thus, the rat and mouse can be used as animal model to apply
osmotic pump and round window catheter to deliver drug, and the
information might be important for human.
A Flexible System for Measurement of the Compound
Action Potential and Otoacoustic Emissions
*John S. Oghalai
, Department of Otolaryngology-HNS, University of
California – San Francisco, 400 Parnasus Avenue, Suite A730,
San Francisco, CA 94143-0342
The compound action potential and otoacoustic emissions are
commonly used measurements when assessing cochlear function in
hearing research. However, the equipment setup required to do this
either involves complicated in-house hardware and software
development or the use of commercial equipment that often has limited
flexibility. A software algorithm was designed to measure the
compound action potential threshold, distortion product otoacoustic
emissions, and the ipsilateral medial olivocochlear reflex response in
guinea pigs. The software was written in MATLAB code and is run
through a graphical user interface. This interface permits easy control
of the frequency and amplitude ranges, as well as trial and repetition
parameters. There is on-line graphical feedback representation of the
electrophysiologic responses, to permit active user manipulation of the
stimulus parameters as required. Data is stored in text files that are
easily accessible for analysis by MATLAB, EXCEL, or other graphical
software. A laptop computer runs the software, and drives Tucker-
Davis Technology system III hardware via USB cable. The benefit of
this system over what is currently available is that it is portable between
different computers, can be run by less experienced personnel, and
allows great flexibility in stimulus and recording parameters. This
experimental setup could be easily adapted to most multi-user
Trigeminal Ganglion Effects on Neurons in the
Cochlear Nucleus.
*Susan E. Shore
, Jianzhong Lu
Kresge Hearing Research Institute,
University of Michigan, 1301 East Ann Street, Ann Arbor, MI
Otolaryngology, University of Michigan, Ann Arbor, MI
The trigeminal ganglion sends a projection to the ventral cochlear
nucleus (VCN) of the guinea pig (Shore et. al., J. Comp. Neurol.
419:271-285) and to the cochlea (Vass et al., Neuroscience 84: 559-
567). The synaptic terminals of the VCN projection end in the
granule and magnocellular regions. We investigated the function of
these pathways on VCN activity by electrically stimulating the
trigeminal ganglion while recording spontaneous activity from neurons
in the VCN.
A concentric, bipolar stimulating electrode was placed stereotaxically
into the ipsilateral trigeminal ganglion (0.37 cm caudal to bregma, 0.45
cm lateral from the midline and 1.3 cm ventral to bregma). Electrical
stimuli were applied as bipolar pulses, 100 ms per phase, at intervals of
200 ms. Current amplitudes ranged from 10-100 mA. After aspirating a
portion of the cerebellum overlying the cochlear nucleus, responses
from single units were obtained using a single shank, 16-channel
electrode to enable simultaneous recordings multiple neurons. The
majority of units recorded in the anteroventral and posteroventral
divisions of VCN showed a complex response to trigeminal ganglion
stimulation, consisting of an inhibitory phase followed by two
excitatory phases. A small percentage of units showed no change, or
decreased spontaneous rate. After applications of neomycin sulphate to
the cochlear fluids, to eliminate the cochlear portion of the pathway, the
excitatory components disappeared, leaving only an inhibitory
component. Removing the cochlear portion of the pathway thus resulted
in net inhibition of VCN units, suggesting that the trigeminal
innervation of the cochlea is excitatory to VIIIth nerve fibers.
These results demonstrate that a projection from a predominantly
somatosensory ganglion can influence the activity of second-order
auditory neurons, and may play a role in integration mechanisms
involving the cochlea and its central targets.
Effects of Trigeminal Ganglion Stimulation on the
Central Auditory System.
*Hussam El-Kashlan
, Shore Susan, Otolaryngology, University of
Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-
A projection from the trigeminal ganglion to the ventral cochlear
nucleus (VCN) of the guinea pig was recently described (Shore et. al., J.
Comp. Neurol. 419:271-285). The synaptic terminals of this projection
end in the granule and magnocellular regions of the VCN. We
investigated the effect of electrically stimulating the trigeminal ganglion
on the central auditory system activity using 2-deoxyglucose (2-DG)
autoradiographic techniques.
Guinea pigs were anesthetised with ketamine and Rompun and held in
a stereotaxic device. Rectal temperature was monitored and maintained
at 38∞ + 0.5∞C. The bone overlying the cerebellum and posterior
occipital cortex was removed to allow stereotaxic placement of a
concentric, bipolar stimulating electrode into the ipsilateral trigeminal
ganglion (0.37 cm caudal to bregma, 0.45 cm lateral from the midline
and 1.3 cm ventral to bregma). Electrical stimuli were applied as
bipolar pulses, 100 ms per phase, at intervals of 200 ms and amplitude
of 100 mA. Control animals were not stimulated. 2-DG was
administered by intramuscular injection. Following a 1-hour
incorporation period, animals were sacrificed, the brains rapidly
harvested, and prepared for autoradiography using standard techniques.
Autoradiographs were analyzed using a computer-assisted video
densitometry to determine film optical density in the central auditory
regions of interest. The cerebellum was also sampled as a grey matter
indifferent intra-brain control region.
Results showed systematic and significant differences between 2-DG
uptake in the cochlear nucleus ipsilateral to trigeminal ganglion
stimulation when compared to the contralateral side. Differences also
were found between control and stimulated animals. These results
demonstrate that a projection from a predominantly somatosensory
ganglion can influence the activity of second- and higher order auditory
Interactions of excitatory and inhibitory synaptic
inputs in the MSO.
*Kevin Rowland
, George A. Spirou
Physiology, West Virginia
University, Morgantown, West Virginia 26506,
Neuroscience Research Center, Dept. of Otolaryngology, West
Virginia University School of Medicine, Morgantown, WV
The medial superior olive (MSO) is a stack of bipolar neurons involved
in sound localization. We investigated membrane properties of MSO
cells in 4-15 day old gerbil brain slices, by using patch electrodes.
Resting membrane potential (RMP) decreased linearly with age; at 4-9
days the average RMP was ñ44 mV, at 10-15 days the average RMP
was ñ52 mV. MSO cells exhibited non-linear current vs. voltage (I-V)
curves, with lower input resistance at depolarized voltages (206 vs. 164
Mohms). MSO cells were filled with lucifer yellow and neurobiotin
and visualized after fixation by using immunocytochemistry. Well-
filled cells were reconstructed in 3D using Neurolucida, modeled as

ARO Abstracts 7 Volume 25, 2002
cylinders and imported into a neuronal simulation program (NEURON).
The membrane of the model MSO cell was outfitted with Hodgkin-
Huxley type sodium and potassium channels, and low-threshold
potassium channels. Excitatory inputs were placed on the midway point
of all second order dendrites. Interaural temporal delays (ITDs) were
simulated by activating (at 100 Hz) one side of the cell prior to the other
while recording EPSPs in the cell body of the model cell. ITD curves
revealed half-maximal activation at 400 usecs ITD. EPSPs recorded
from the model cell were imported into recording software (Clampex)
and injected into a living MSO cell. Electrical activation of the MNTB
and LNTB elicited IPSPs in MSO cells in the presence of glutamate
receptor blockers (CNQX, APV and MK-801). IPSPs reversed at ñ87
mV and decayed with an average time constant of 2.4 msecs. In a few
MSO cells, we coupled MNTB stimulation with injection of simulated
binaural excitation through the recording pipette. Inhibitory inputs
delayed MSO cell activation from the beginning EPSP cycles to later in
the EPSP train. We are exploring the effects of temporal interactions of
inhibitory and excitatory inputs on MSO activity patterns.
Supported by NSF grant IBN 9728933.
Trigeminal Projections to the Cochlear Nucleus in Rats
*Charles-Andre Haenggeli
, John R. Doucet
, David K Ryugo
Otolaryngology, Johns Hopkins University, Baltimore, MD
Otolaryngology- Head and Neck Surgery, Johns Hopkins
University School of Medicine, 720 Rutland Avenue, Baltimore,
MD 21205
The auditory system has long been known to participate in cross-
modality interactions, including those with somatosensory functions. It
has been hypothesized that some somatosensory afferents provide
information related to pinna and head position for the purpose of
localizing a sound source in space (Y
oung et al., J.Neuro
1995). It has also been speculated that somatosensory pathways which
project into the auditory system are involved in the modulation of
tinnitus (Levine, Am.J.Otolaryngol., 1999). One target of these
somatosensory projections is the granule cell domain (GCD) of the
cochlear nucleus (Wright and Ryugo, J.C.N., 1996). The GCD receives
highly diverse inputs and projects to the dorsal cochlear nucleus(DCN),
which in turn projects to higher auditory structures. Thus the GCD
emerges as a multimodal, integrative nexus within the auditory system,
and our goal is to identify the origin of cells projecting to it. This study
focuses on inputs to the GCD from the trigeminal sensory complex.
The fluorescent retrograde tracer Fast-Blue was injected into the GCD
lamina in 11 rats. After a 5-6 day survival period, the distribution of
labeled cells was determined throughout the brain. Four rats did not
exhibit injection sites limited to the cochlear nucleus and were thus
discarded. In all remaining rats, labeled cells were observed in the
trigeminal nuclear complex as well as the vestibular nuclei, gracile and
cuneate nuclei, and pontine nuclei. The spinal trigeminal nuclei (pars
caudalis,interpolaris, and oralis) contained many labeled cells,
predominantly ispilateral to the injection site and mostly in pars
interpolaris. Anterograde tracing experiments are underway to
determine the synaptic nature of the projections. These data may
provide a morphological substrate to observations of somatosensory
influences in the perception of tinnitus.
Supported by NIH grants DC00232,DC04395,and DC04505 and the
Schweizerische Stiftung fur Medizin und Biologie
Synapses and Postsynaptic Targets of Type II Auditory
Nerve Fibers in the Granule-Cell Lamina of the Mouse
*Thane E. Benson
, M. Christian Brown, Eaton-Peabody Laboratory,
Massachussetts Eye & Ear Infirmary, 243 Charles St., Boston,
MA 02114
Type II auditory nerve fibers provide the afferent innervation of outer
hair cells in the cochlea and project to the cochlear nucleus. The
synaptic ultrastructure and postsynaptic targets of type II endings in the
cochlear nucleus are not well known. We examined type II endings in
the neuropil adjacent to the granule cell lamina (between the ventral and
dorsal divisions of the cochlear nucleus), because in this area the
swellings of type II axons become angular and complex-shaped and
because the more numerous type I axons do not project here. Type II
axons were labeled by extracellular injections of HRP into the cochlea
of 4 mice, 7 type II axons were first drawn using the light microscope,
and then portions of these fibers in the lamina were studied with serial-
section electron microscopy.
A total of 27 synapses were observed, most commonly from angular or
pedunculated en passant swellings, but not from ellipsoidal swellings or
intra-swelling sections of the axons. Type II synapses are relatively
simple–they had few, round vesicles, a synaptic cleft, and a meager
postsynaptic density. The most frequent target was small dendrites or
their spines; the soma of origin of these dendrites could not generally be
identified. However, one small cell in the lamina with 3 small dendrites
was a target, receiving a type II synapse on a proximal dendrite
swelling. A less common target was large dendrites; although these
dendrites could not generally be identified, somatic type II synapses
were seen in 2 mice onto five moderately large neurons that produced
large dendrites. These cells were located on the VCN edge of the
lamina. Some large-dendrite targets had other, unlabeled synapses with
postsynaptic bodies, suggesting that they also r
eceive i
nput from
branches of medial olivocochlear axons. Overall, these results suggest
that type II endings in the granule-cell lamina convey information to
several types of neurons in the cochlear nucleus.
(Supported by NIDCD RO1 DC01089)
Three-dimensional Reconstruction of Synaptic
Structures in the Small Cell Shell of the Cochlear Nucleus.
*Brandon Hollis Poe
, Jonathan Larson, D. Kent Morest, Department of
Neuroscience, University of Connecticut Health Center, 263
Farmington Ave., Farmington, CT 06030-3401
Still a challenge to current views of synaptic function, the synaptic nest
was originally described in the medial geniculate body (Morest, 1971)
as an aggregation of serial synaptic junctions without glial apposition,
clearly distinguished in their structure from the glomeruli of the
cerebellum and olfactory bulb. Similar structures, described variously as
nests, glomeruli, or mitts, have been reported. The prevalence of such
structures in the small cell shell of the cochlear nucleus provides an
opportunity to analyze the key features of their synaptic organization in
a relatively coherent region. Adult mice were perfused with an aldehyde
fixative. Blocks were dissected from 200
m thick coronal vibratome
sections, osmicated, embedded in epon, and trimmed to 0.5 mm
Serial thin (700 ≈) sections were mounted in ribbons on sequential
Formvar-coated slot grids. Serial photographic negatives were digitized
for analysis with software developed at Boston Univ.
( Reconstructions clearly differentiated
individual synaptic sites apposed by glial processes from nest-like
structures. The glomerulus (micronest) is organized around a single
excitatory mossy fiber terminal without glial investment but flanked by
terminal dendritic processes. The synaptic nest (macronest) is an
accretion of many axonal terminals organized around at least one
prominent dendrite and several smaller dendritic processes, all in direct
contact without glial investment. Previously, we have reported
(Josephson & Morest, 2000) that synaptic nests, especially macronests,
lack high-affinity glutamate transporters suggesting an enhanced
capacity to accumulate extracellular excitatory transmitter. If so, the
nests may process neural information differently than classical
synapses. Nests may also respond differently to overstimulation.
NIH grant support T32DC00025 and R01DC00127.

ARO Abstracts 8 Volume 25, 2002
Functional Input from the Inferior Colliculus to
Cochlear Nucleus Neurons: an in vitro Whole Brain Study
*Alexander Babalian
, Anne-ValÈrie Jacomme
, David K Ryugo
, Eric
M. Rouiller
Institute of Physiology, University of Fribourg,
Rue du MusÈe 5, Fribourg, Fribourg CH-1700 Switzerland,
Otolaryngology – Head and Neck Surgery, Johns Hopkins
University School of Medicine, 720 Rutland Avenue, Baltimore,
MD 21205
In addition to external acoustic information coming from auditory nerve
(AN) fibers, the cochlear nucleus (CN) receives feedback i
nputs from
central auditory structures and projections from non-auditory sources.
The existence of these projections suggests an important role of
auditory and non-auditory inputs in shaping the response properties of
CN neurons, which in turn must subserve some fundamental functions.
One of the major descending auditory pathways to CN neurons
originates in the inferior colliculi (IC). However, the effects of this
input on CN neurons are unknown. In the present study, using the
isolated whole brain (IWB) preparation of the guinea pig, we directly
assessed physiological responses of intr
acellularly recorded and stained
CN cells to electrical stimulation of the IC. Stimulation of the
contralateral IC evoked both excitatory (EPSP) and inhibitory (IPSP)
postsynaptic potentials in CN cells as well as antidromic activation of
some cells. Synaptic responses were observed in principal cells of all
three subdivisions of the CN indicating a widespread influence of IC
inputs onto the CN. The latencies of EPSPs and IPSPs were in the range
of 5 – 9 ms suggesting oligosynaptic (di-, and trisynaptic) transmission.
We propose that excitatory transmission to principal CN cells operate
via direct IC projection to CN granule cells, whereas the inhibitory
responses could be mediated by IC projections to ventral periolivary
nuclei which project in turn to the CN. Additional experiments are
needed to test the hypothesis for two distinct IC pathways exerting
opposite effects on principal CN cells.
Supported by Swiss National Science Foundation (grant No.31-
055836.98) and NIH/NIDCD grants DC00232 and DC04395.
3-Dimensional Reconstructions of Cochlear Nucleus
Neurons in Guinea Pigs: Structure-Function Relationships
Revealed in the
in vitro
Whole Brain Preparation.
, Anne-ValÈrie Jacomme
, Eric M. Rouiller
Alexander Babalian
, David K. Ryugo
Department of
Neuroscience, Johns Hopkins University School of Medicine, 725
N. Wolfe St., Baltimore, MD 21205,
Institute of Physiology,
University of Fribourg, Fribourg, Fribourg Switzerland,
Otolaryngology-HNS and Neuroscience, Johns Hopkins
University School of Medicine, 720 Rutland Avenue, Baltimore,
MD 21205
Our goal in this project was to reveal structure-function relationships in
the cochlear nucleus by correlating the 3-dimensional structure of
individual neurons with their physiological responses to various inputs.
We used the in vitro whole brain preparation of the guinea pig to
intracellularly record and stain neurons in the cochlear nucleus
(Babalian et al., NeuroReport, 10:1913, 1999). While recording
intracellularly, we tested the synaptic responses of CN neurons to
electrical activation of inputs from
each auditory nerve, the ipsilateral
dorsal column nuclei, and the ipsilateral trigeminal nerve. At the end of
each experiment, the brain was perfused with 4% paraformaldehyde,
sectioned, and histologically processed using standard ABC procedures.
We made 3-dimensional reconstructions of these neurons using a light
microscope and computer software (Neurolucida v4.33). In this way,
we were able to relate dendritic orientation, and physiological response
properties to overall structure of the nucleus. Among the cell types
reconstructed were multipolar, and octopus cells in the VCN. Octopus
cells could be distinguished physiologically and structurally from other
cell types: they never responded to dorsal column or trigeminal nucleus
stimulation, exhibited ìgradual spikesî and were oriented orthogonal to
the isofrequency planes. Multipolar cells were of 2 basic types that
could be determined accurately through 3-dimensional reconstructions:
planar cells have their dendrites oriented parallel to the incoming
auditory nerve fibers, whereas radiate cells have their dendrites lying
across the path. Planar cells exhibit smaller IPSPs following
stimulation of the ipsilateral auditory nerve compared to radiate cells,
although there was no dramatic difference in their responses to
somatosensory stimulation.
Supported by NIH/NIDCD grant DC00232, NIH grant T32 MH20062,
and the Swiss National Science Foundation (grant No.31-055836.98).
Projections of Multipolar Neurons in the Ventral
Cochlear Nucleus to the Lateral Superior Olive in Rats
*John R. Doucet
, David K. Ryugo
Otolaryngology-HNS, Johns
Hopkins University School of Medicine, 720 Rutland Avenue,
Baltimore, MD 21205,
Otolaryngology-HNS and Neuroscience,
Johns Hopkins University School of Medicine, 720 Rutland
Avenue, Baltimore, MD 21205
We are studying two types of multipolar neurons in the ventral
cochlear nucleus (VCN) of the rat: planar cells and radiate cells. Planar
cells have dendrites oriented parallel to VCN isofrequency sheets and
project tonotopically to the dorsal cochlear nucleus (DCN). Radiate
cells have dendrites oriented perpendicular to the isofrequency planes
and project broadly to the DCN. In this study, we examined the
projections of these neurons to the superior olivary complex. An
extracellular injection of biotinylated dextran amine (BDA) was made
into the DCN of each rat. After histological processing, we observed a
mediolateral stripe of BDA-filled structures in the VCN that included
planar cells. The stripe was in tonotopic register with the injection site.
Labeled radiate cells were scattered across the tonotopic axis. We also
observed a prominent stripe of labeled axons and terminals in the
ipsilateral lateral superior olive (LSO) that was oriented parallel to the
plane of isofrequency sheets. Our interpretation is that the LSO stripe is
due to BDA being anterogradely transported by planar cell axons to
their terminals. First, cutting the dorsal acoustic stria after the DCN
injection (severing the DCN projection axons) failed to abolish labeling
in the LSO. Second, thin collaterals from planar cell axons in the
trapezoid body terminated in the stripe. Third, the position of the LSO
stripe was systematically and topographically related to the position of
the DCN injection site. Collectively, these observations imply that
planar cells project tonotopically to the LSO. Multipolar cells correlate
with the physiological class referred to as choppers, and choppers are
thought to encode stimulus intensity. Our hypothesis is that planar cells
provide intensity information to LSO cells that is used to compute
interaural level differences for localizing sounds in space.
Supported by NIH grants RO1DC00232, RO1DC04395, and
Bidirectional synaptic plasticity in the dorsal cochlear
*Kiyohiro Fujino
, Donata Oertel, Department of Physiology, University
of Wisconsin Medical School, 1300 University Avenue, Madison,
WI 53706
The superficial layers of the dorsal cochlear nucleus (DCN) resemble
the cerebellum and the sensory lobe of the electric fish (Mugnaini et al.
1980; Bell et al. 1997). Plasticity at parallel fiber synapses in these
structures controls the gain of synapses at the interface between sensory
and motor pathways. Cerebellar Purkinje cells show long-term
depression (LTD) (Ito et al., 1982). Principal cells in the electric fish
show both long-term potentiation (LTP) and LTD (Bell et al., 1997).
Our results indicate that there is bidirectional plasticity at the
glutamatergic synapses between parallel fibers and their targets in the
mammalian DCN.
Whole-cell, voltage-clamp recordings were made from cartwheel and
fusiform cells in coronal slices from mice. LTP was induced by high-

ARO Abstracts 10 Volume 25, 2002
Distribution Of Glutamate Receptors In The Cochlear
Nuclei In Mice Lacking The AMPA Receptor Subunit,
*Ronald Sebastian Petralia
, Ya-Xian Wang
, Bryce Vissel
, Nathalie
, Gordon A. Royle
, Konrad Noben-Trauth
, Stephen F.
, Robert J. Wenthold
Lab. Neurochemistry,
NIDCD/NIH, 50 South Dr. MSC 8027, Bethesda, MD 20892-
Mol. Neurobiol., The Salk Institute, La Jolla, CA ,
NIDCD, NIH, 5 Research Court, Rockville, MD 20850
AMPA-ionotropic glutamate receptors (AMPARs; 4 subunits, GluR1-4)
mediate fast transmission in the CNS. These receptors are calcium
permeable when GluR2 is absent. Since calcium acts as a 2nd
messenger to potentiate synaptic responses, changes in AMPAR
composition can alter normal synaptic function. AMPARs in synapses
on spherical bushy cells of the anteroventral cochlear nucleus (AVCN)
contain no GluR1, low GluR2 and high GluR3-4. In outer layers of the
dorsal CN (DCN), synapses on apical dendrites of fusiform cells have
only GluR2-3, while cartwheel cell dendrite synapses have all 4
subunits. The latter 2 synapses also have high delta GluRs. Outside of
the DCN, such high levels are seen only in Purkinje cell synapses in
cerebellum. In the AVCN of the GluR2 mutant (KO), levels of
immunogold labeling for GluR2/3 antibody remain about the same as in
wild type (WT) synapses. This is expected since only low GluR2 is
found in normal animals, so that antibody labeling reflects mainly levels
of GluR3; the latter apparently do not change much in KOs. In contrast,
a significant decrease in GluR2/3 labeling (WT-0.82 [n=194] vs. KO-
0.30 [n=141] gold/synapse) is seen in synapses of the KO outer DCN;
this is expected since, in normal animals, these synapses contain
substantial levels of GluR2. Interestingly, in these synapses, levels of
delta increase significantly in the KO (WT-2.25 [n=165] vs. KO-3.04
[n=136] gold/synapse; or 7.76 vs. 11.69 gold/μm). A similar increase is
seen for delta receptors in synapses of the cerebellum (Petralia et al.,
Soc. Neurosci. Abs. 2001), where delta receptors are involved in LTD
in normal animals. Thus, we predict that synaptic function in the AVCN
changes little in KOs, while profound changes are expected in the DCN.
Also, the increase in delta receptors in KO synapses suggests that lack
of GluR2 has altered the regulation of glutamate receptors.
The effect of random maskers on comodulation
masking release in the cochlear nucleus
*Jesko L Verhey
, Ian M. Winter, Physiology, University of Cambridge,
Cambridge, Cambridgeshire United Kingdom
Masking of a sinusoidal signal is considerably less when the masker has
coherent level fluctuations across-frequency. This effect is called
comodulation-masking release (CMR). In a r
ecent study (Pressnitzer D.,
Meddis, R., Delahaye, R., and Winter, I.M. 2001, J. Neuroscience, 21,
6377-6386), using amplitude-modulated tones as the masker, it was
shown that the responses of some units in the ventral cochlear nucleus
of the guinea pig are consistent with the psychophysical CMR effect.
This study investigates, if the type of neurons that showed CMR with
amplitude-modulated tones as the maskers also show a CMR-like effect
when noise maskers were used instead. In contrast to amplitude-
modulated tones the noise masker waveforms will be different for
presentation. The experiments were performed on pigmented guinea
pigs, anaesthetised with Urethane (1.5g/kg) and supplemented with
Hypnorm (1 mg/kg). The target signal was a pure tone signal at the
unit’s BF. Three different conditions were investigated. In a reference
condition, the masker was a 20-Hz noise band centred at the signal
frequency (on-frequency band). In the comodulated and the deviant
condition, the masker consisted of the on-frequency band and several
flanking bands above and/or below the BF. In the comodulated
condition all noise bands had the same temporal level variations
whereas in the deviant condition the level variations were independent
of each other. The response was measured for different signal-to-noise
ratios. With non-deterministic maskers 25% of the units showed
considerably higher d’ values for the comodulated condition than in the
deviant or reference conditions at the same signal-to-noise ratio. These
units were classified as choppers or low-frequency units. In our current
population of units, if the response of the unit showed the CMR effect
with the deterministic masker, it also showed CMR with the non-
deterministic masker.
Responses to Combinations of Tones in the Cochlear
Nucleus of Awake Mustached Bats
Robert A Marsh, *
Jeffrey J. Wenstrup
, Department of Neurobiology
and Pharmacology, Northeastern Ohio Universities College of
Medicine, 4209 St. Rt. 44, PO Box 95, Rootstown, OH 44272
Acoustic behaviors including orientation and social communication
depend on neural integration of information across the sound spectrum.
Spectral integration is performed by combination-sensitive neurons,
which show time-sensitive interactions (facilitatory or inhibitory)
between distinct acoustic elements in complex signals. In the mustached
bat (
Pteronotus parnellii
), combination-sensitive neurons are abundant
in the inferior colliculus (IC). Facilitatory combinations-sensitive
neurons are thought to be created in the IC, but the origin of inhibitory
interactions is unclear. Because CN neurons project to combination-
sensitive neurons in the mustached batís IC, we examined whether
neurons in the CN display the same combination-sensitive response
properties that occur frequently in the IC. Using tracer-filled
micropipettes and stereotaxic procedures, we recorded single unit
responses in awake mustached bats to tones, noise, or combinations of
tones or noise. Results are from 64 singles units localized to the three
major divisions of the cochlear nucleus. The majority of neurons (36
units) were tuned to a single frequency band, with little evidence of
two-tone interactions. Twenty-three percent (15 units) showed multi-
peaked tuning curves. Twenty percent (13 units) showed inhibitory
interactions that could not be described as sideband inhibition. No units
showed facilitatory interactions similar to those observed in the IC. The
multi-peaked tuning curves and inhibitory spectral interactions were
found in all major subdivisions. These results demonstrate that
spectrally complex response properties occur throughout the CN.
However, the frequency range of interactions was different than what
occurs among the majority of combination-sensitive neurons in the IC.
This suggests that facilitatory and most inhibitory combinatorial
response properties in the IC are created above the CN.
(Supported by National Institute on Deafness and other Communication
Adaptation of evoked near-field potentials of the
cochlear nucleus in response to pulsatile acoustical
stimulation in awake rats.
Eric M. Rouiller, *
GÈrard Loquet
, Department of Physiology,
University of Fribourg, Musee 5, Fribourg, FR 1700 Switzerland
In order to study the properties of neural adaptation in response to
acoustic stimulation, near-field evoked potentials were recorded from a
chronically implanted electrode in the cochlear nucleus (CN) of awake
Long Evans rats. Auditory thresholds were measured for each animal
(n=8) and adaptation was investigated with repetitive 50 ms acoustical
clicks delivered in trains of 250 ms duration separated by a silence of
250 ms. Eleven intra-train click rates were tested ranging from 100 to
2000 pulses per second (pps). The amplitude and the occurrence time of
the first negative deflection (N1) of the averaged CN field potential
were determined for each click in the train by using a subtracting
method. As expected, a large response was obtained for clicks at the
onset of the train followed by a fast exponential amplitude decrement
and a plateau. This adaptation process was the more accurately fitted
with a two time constants equation which allowed to describe a rapid, a
short-term and the beginning of a long-term adaptation. At low click
rate (100 pps), the rapid and short-term adaptation duration
(respectively 24 and 74 ms) and time constants (respectively 6.7 and
41.1 ms) were in line with auditory nerve data (Westerman and Smith,
1984). At rates higher than 1000 pps, these latter constants did not vary

ARO Abstracts 11 Volume 25, 2002
any more, an observation consistent with the absolute refractory period
of the auditory nerve. For rates ranging between 400 and 1000 pps,
constants of adaptation were very close to what was observed above
1000 pps, suggesting that the current adaptation was related to the
relative refractory period of the auditory nerve. In conclusion,
adaptation recorded in the cochlear nucleus well reflects the adaptive
properties of the auditory nerve.
Westerman, L.A. and Smith, R.L., 1984. Rapid and short-term
adaptation in auditory nerve responses. Hear. Res. 15: 249-260.
A Steady-State Auditory Response Evoked from
Dichotic Tones.
*Carolyn Wendy Garnham
, Peter Lampacher, Marcus Schmidt,
Research and Development, MED EL Cochlear Implants, 77a
Fuerstenweg, Innsbruck, Tyrol A6020 Austria
During recent years, a number of cochlear implant users have been
fitted bilaterally. Benefits for adults have been shown to include
improvements in localization ability. Psychophysical tests also suggest
useful binaural processing abilities in at least some patients. Evaluation
of the bilaterally implanted child may be problematic. There is therefore
a possible need for an objective test of binaural processing.
Low frequency tones with differences of a few Hz presented
dichotically elicit a perception of the difference tone (the binaural beats
phenomenon). A search was made in 3 normal hearing subjects for a
steady state evoked potential reflecting this difference frequency. Tone
pairs of the order of 400, 600 and 800Hz were generated digitally. A
trigger was generated digitally every 4
beat, to allow data capture by
an evoked potentials recording system synchronized to the difference
frequency. Recording was carried out with both diotic and dichotic
application of the two tones. All tone pairs investigated elicited a
discernible steady-state potential when applied diotically. Dichotic
presentation yielded a small steady-state potential, discernible with
long-term averaging of several thousand stimuli, at 3Hz and 40Hz
difference frequencies, applied through insert phones at an intensity of
approximately 60dBSL (+/-10dB). This reached an amplitude of 300-
500nV, a factor of approximately 4-5 less than the potential evoked
from the diotic stimulus.
Further studies will evaluate the dependence of the response on stimulus
characteristics. The stimulus might also be encoded and applied through
a cochlear implant, and the response characteristics correlated with
binaural processing. However the test requires long recording times for
the lowest difference frequencies, which may limit its potential
usefulness as a clinical measure of binaural function.
Rapid acquisition of auditory brainstem responses with
high frequency (8-14 kHz) tone burst trains
*Stephen A. Fausti
, A. Bobal, C. Flick, J. H. Henry, C. R. Mitchell,
National Center for Rehabilitative Auditory Research, VA
Medical Center, Portland, OR 97207
Auditory brainstem responses (ABR) to three sequences of tone burst
stimuli were compared in four groups of subjects; two normal hearing
and two sensorineural hearing loss groups (N=20 or 30). The tone burst
sequences were; 1) a single burst; 2) a five-stimulus sequence or train;
and, 3) a fifteen-stimulus train. The tone burst center frequencies were
at 6, 8, 10, 12 and 14 kHz. The ABR Wave V response latency &
amplitude were used to determine the test-retest reliability and the
probability of response detection at different frequencies and levels. For
each sequence
duplicate responses were obtained (in two different
sessions), such that both intra- and intersession reliability could be
determined. Reliability was similar among the three stimulus
configurations. Statistically significant differences (ANOVA) in Wave
V response latency were found between the single and the 15-stimulus
train. The latency delay (about 0.2 ms) from the train indicate the
presence of response adaptation when the frequencies of sequenced
stimuli are closely spaced (1/3 octave or less), however, the significance
of these differences depends upon the intended use of these stimulus
trains. For many purposes these small differences are not biologically
significant. For example, in the detection of ototoxicity, where a subject
serves as their own control, a small amount of response adaptation does
not preclude the use of closely spaced frequencies for serial monitoring.
Stimulus trains are demonstrated to be efficient and suitable for the
rapid acquisition of high frequency ABRs.
Oral presentation only
Audiovisual Requirements: Standard: one slide projector.
C. R. Mitchell, National Center for Rehabilitative Auditory Research,
Department of Veterans Affairs Medical Center, 3710 SW US Veterans
Hospital Road (R&D-NCRAR) Portland Oregon, 97207, USA.
Effects of Stimulus Repetition and Background Noise
on Speech Evoked Auditory Brainstem and Frequency
Following Responses in Normal and Learning Impaired
*Brad Wible
, Trent G Nicol, Nina Kraus, Communication Sciences,
Northwestern University, 2299 North Campus Drive, Evanston,
IL 60208
This study investigated whether auditory brainstem and frequency
following responses (ABR and FFR, respectively) to rapidly presented
speech stimuli, presented in quiet and in noise, differed between normal
and learning-impaired children. Subjects were normal-hearing school-
age children. Normal subjects (NL) scored significantly better than
learning-impaired subjects (LP) on standardized measures of reading
and spelling and on a speech s
ound discrimination task. Responses were
elicited by a 40 ms /d/, presented at 80 dB SPL. Stimuli were presented
in trains of four repetitions, separated by 12 ms within and 30 ms
between trains. Stimuli were presented in quiet and in white noise (S/N
Addition of noise diminished most measures of response amplitude and
synchrony, and increased all measures of response latency. Stimulus
repetition resulted in increased latency of ABR wave V and decreased
RMS amplitude of the FFR. The amplitude of a major FFR peak which
occurred roughly 37 ms post stimulus onset was larger in NL than in LP
subjects. Also, the 200-700 Hz frequency region of the FFR contained
more energy in NL than in LP subjects. This finding, also shown by
Cunningham et al. (2000), is intriguing; the group difference occurs in
the same spectral region as does the first formant (F1) in stimuli along
the /da/-/ga/ continuum. This stimulus component is crucial to
behavioral discrimination. The amount of energy in the FFR over this
spectral region correlated with behavioral discrimination along the /da/-
/ga/ continuum.
Supported by NIH R01DC01510 and T32DC0001517.
Hearing in “primitive” fish: brainstem responses to
pure tone stimuli in the lake sturgeon, Acipenser fulvescens.
*Michaela Meyer
, Arthur N. Popper, Department of Biology,
University of Maryland, College Park, MD 20742
We investigated the auditory capabilities of the lake sturgeon,
Acipenser fulvescens. Sturgeon belong to the Acipenseriformes, an
ancient group of fishes that arose early in the evolution of bony fish
(late Triassic period). The purpose of this study was to test the
hypothesis that basic functions of the auditory system developed very
early in vertebrate evolution. We also selected lake sturgeon because
the gross morphology of it’s ear resembles that of teleost fishes and
other vertebrates.
To test the hearing capabilities of lake sturgeon, we recorded auditory
evoked potentials to pure tone stimuli of varying frequency and
intensity using the auditory brainstem response (ABR) method. Our
data show that lake sturgeons detect pure tones from 100 to 2000 Hz,
with best sensitivity from 100 to 400 Hz.

ARO Abstracts 12 Volume 25, 2002
We compared the sturgeon ABR data with responses obtained in two
different species of teleosts, the oscar (Astronotus ocellatus) and the
goldfish (Carassius auratus), using the same setup and data analysis as
used in the sturgeon. The ABR data for the lake sturgeon are more
similar to the goldfish, a hearing specialist that can hear up to 5000 Hz,
than to the oscar, a hearing non-specialist that can only detect sound up
to 400 Hz. Best frequencies of the goldfish are between 600 Hz and
1000 Hz, which is higher than the lake sturgeon. Whether the lake
sturgeon can be considered specialized for hearing needs to be
investigated further, particularly with respect to a potential relationship
between the ear and any peripheral sound detecting structure. This
result is of evolutionary interest since the lake sturgeon (belonging to an
ancient group) seems to share brainstem response characteristics with
teleosts, that are a highly successful and diverged group of fish. This
indicates similar functions of the auditory system may already be found
early in vertebrate history.
Brainstem Responses of American Shad, Alosa
sapidissima, to Ultrasound
*Dennis T.T. Plachta
, Arthur N. Popper, Department of Biology,
University of Maryland, College Park, MD 20742
Many toothed cetaceans use high frequency clicks (40-
120 kHz) to
identify objects in their environment, including prey. A number of
species of clupeid fishes (herrings, menhaden and shads), are able to
detect ultrasonic sounds to well over 100 kHz (e.g. Mann et al., 2001)
suggesting that this ability evolved to avoid predation by marine
mammals. However, the mechanism of ultrasound detection in these
fish is still not understood. In this study, we investigated the response of
brainstem nuclei of an ultrasound detecting species, the American shad,
Alosa sapidissima, to learn about its response of ultrasonic versus sonic
sound reception. American shad were presented with pure tone stimuli
of 100 ms duration 20 dB above hearing threshold. Twenty-two units
were recorded in eight experiments (14 multiunit and 8 single units).
The units show several kinds of responses including tonic, phasic, and
tonic-phasic. Twelve units responded in a phasic fashion to the
stimulus, with two single units showing ON and OFF responses and two
others showing inhibition during stimulation. Since ultrasound was used
as a search stimulus, no purely sonic units were recovered. None of the
units responded to frequencies below 10 kHz. Two types of units were
found. One type responded to low ultrasound and sonic frequencies
from 10 to 20 kHz, while the other type responded to sounds from 60
kHz to 97 kHz, with the strongest responses at 80 and 90 kHz. There
does not seem to be any continuum for the whole ultrasound range in
any unit. Since behavioral data (Mann et al. 1997) showed that
American shad can detect a much wider range of frequencies than found
in the units recorded, it is possible that different ultrasound frequencies
are represented in different units, or different regions of the brain. There
does not appear to be common processing of sonic and ultrasonic sound.
This gives rise to the questions about which sensory organ is
responsible for ultrasound detection.
A neural model for binaural coincidence detection
using both excitation and inhibition
*Yi Zhou
, H. Steven Colburn, Hearing Research Center and Department
of Biomedical Engineering, Boston University, 44 Cummington
Street, Boston, MA 02215
The Jeffress model implies that the maximum of the rate-ITD curve is
determined by the coincidence of excitatory inputs and the minimum by
the dis-synchrony of the inputs. Although models of MSO activity can
match available in-vivo data with purely excitatory inputs (Han and
Colburn, Hear. Res. 1993), a variety of evidence indicates the presence
of inhibition in these cells. This study explores the possible role of
temporally synchronized inhibitory inputs within a multi-compartment
model similar to that of Simon et al.(ARO 1999). Initial work focuses
on comparisons between responses to low-frequency (100-1000 Hz)
periodic stimuli that are in-phase, out-of-phase, and monaural. With
only excitatory inputs and no spontaneous activity, firing rates
consistently varied from lowest to highest for monaural, out-of-phase
and in-phase inputs, respectively. Adding periodic inhibitory inputs
with fixed delays D relative to the excitation, we found that rates for the
out-of-phase case can drop below those for the monaural case only for a
narrow range of D values. Further, if D was held constant while the
frequency varied, we found that most out-of-phase rates dropped but
only those frequencies that were “matched” with the delay were lower
than the monaural rate. The rate-ITD curve exhibited an increase in
sharpness and in some cases the peak rate was non-monotonic with the
frequency of inputs (as opposed to the curve without inhibition). This
study raises the question of whether the delay D varies with CF and
whether the reduction of the out-of-phase rate relative to the monaural
rate would depend on the frequency of the inputs.
[Supported by NIH.]
Responses Of Ferret Superior Colliculus Neurons To
Stimuli Presented In Virtual Acoustic Space
*Robert AA Campbell
, Tim P Doubell, Fernando R Nodal, Jan WH
Schnupp, Andrew J. King, Physiology Dept., University of
Oxford, Oxford, Oxfordshire United Kingdom
Auditory localization depends on the processing of monaural and
binaural spatial cues. Traditionally, studies of auditory localization have
involved presenting sounds from a speaker in free space or directly to
the ears via headphones. More recently, virtual acoustic space (VAS)
stimuli have been employed in both psychophysical and
neurophysiological experiments. Such stimuli allow faster and more
detailed mapping of the spatial response properties of auditory neurons.
In addition, the sound signal may be manipulated digitally, so that the
contribution of different acoustic cues can be assessed independently.
The superior colliculus (SC) in the midbrain is of interest because it is
one of the few brain areas to contain a neural map of auditory space.
Previous studies have emphasized the role of monaural spectral cues
and interaural level differences (ILDs) in constructing this map in the
mammalian SC. Interaural time differences (ITDs) are generally
thought not to be involved. We investigated this issue by mapping
auditory spatial response profiles of deep layer SC neurons in
anesthetized ferrets, using VAS stimuli generated from the animal’s
own ears. Most SC neurons were broadly tuned within the contralateral
hemifield and their receptive fields expanded with increasing sound
level. In keeping with the results of free-field studies, the speaker angle
producing the best response was fairly well aligned with the visual
receptive field of superficial layer units mapped in the same electrode
penetration, and both varied systematically along the rostrocaudal
extent of the SC. Auditory responses were also examined with VAS
stimuli that had ITDs set to an inappropriate value while the remaining
cues were allowed to vary naturally. This had no clear effect on the
units’ best position or response magnitude. Our findings confirm that
sensitivity to ITDs does not contribute to the map of sound azimuth in
the SC, which is presumably based on ILDs and spectral cues.
Responses of Auditory Cortical Neurons Sensitive to
Interaural Time Differences (ITDs) to Changes in Interaural
*Douglas C Fitzpatrick
, Charles S Ebert, Hoke W Pollock, James M
Pearson, William D Crocker, Otolaryngology and Head and Neck
Surgery, University of North Carolina at Chapel Hill, Chapel Hill,
Sensitivity to ITDs, a major cue for sound localization, can be more
broadly described as sensitivity to interaural correlation. Consequently,
the responses of ITD-sensitive neurons to changing interaural
correlations are of interest. Previous reports have described such
responses at the level of the IC and below in anesthetized animals. For
this study, we recorded responses in the auditory cortex of
unanesthetized rabbits.For each neuron, we first identified the tuning to
ITDs using noise and binaural beat stimuli. These allowed us to identify
a best and worst ITD and the responses as peak-, trough- or

ARO Abstracts 13 Volume 25, 2002
intermediate-type. We then measured the response to changes in
interaural correlation at the best and worst ITDs. As in the IC of owls
(Albeck and Konishi, J. Neurophys, 74:1689-1700, 1995), some
neurons had linear responses to interaural correlations that varied from
+1.0 to -1.0, and others had non-linear responses that could be
described as parabolic or ramped. When tested at best ITD, both of the
non-linear types reached a minimum of firing as the correlation
approached zero and the response declined slowly if at all for negative
correlations. The responses at the worst ITD were usually the reverse, in
that they had a maximum response at a correlation of -1.0 that declined
to a minimum by zero correlation with little or no further change for
positive values of correlation. The correlation values where the
responses became asymptotic varied considerably across non-linear
neurons. For most neurons of both peak and trough type the response at
the best ITD and a correlation of 1.0 was greater than the response at
worst ITD and a correlation of -1.0. In a few the reverse was true.
The greater effect of correlation on the best compared to the worst ITD
suggests that the peaks provide a more salient cue for correlation than
the troughs.
Supported by NIH grant DC03948 and the DRF.
Sensitivity of Inferior-Collicular Neurons to Interaural-
Phase Difference (IPD) in the Presence of Preceding Sound
with Various IPD
*Shigeto Furukawa
, Katsuhiro Maki
, Hiroshi Riquimaroux
, Makio
NTT Communication Sci. Labs, NTT Corp., Atsugi,
Kanagawa 243-0198 Japan,
Dept. Knowledge Eng. & Comp.
Sci., Doshisha Univ., Kyotabane, Kyoto, 610-0321 Japan
Psychophysical studies have shown the localization aftereffect (LA;
e.g., Kashino & Nishida, 1998; Carlile et al., 2001): The perceived
location of a signal is biased away from the location of a preceding
sound with relatively long duration. The present study examined neural
sensitivity to interaural-phase difference (IPD) in the inferior colliculus
(IC), using stimuli that were relevant to conditions that would produce
psychophysical LA. We recorded activities of single-units or multi-unit
clusters with low best frequencies (BFs;
1500Hz) from the IC of the
anaesthetized gerbil. Binaural stimuli were presented to the animal,
each of which consisted of a sequence of the
and the
a brief (typically 10 ms) gap between them. The adapter and the probe
were BF-tone bursts with 200- and 50-ms durations, respectively, at 20
dB above the unit threshold. The adapter and the probe varied
independently in IPD. In control conditions, the probe was presented
alone. Generally, the adapter reduced the spike rates for the probe. For
units with relatively large IPD selectivity (i.e. large spike-rate
modulation by the probe IPD in control conditions), the reduction of the
probe-driven responses tended to increase with decreasing separation of
the adapter IPD and the unit’s best IPD. For units with little IPD
selectivity, the presence of the adapter unchanged or increased
somewhat the IPD selectivity. Overall, it appeared that not the adapter
per se
, but the strength of adapter-driven responses accounted well
for the reduction size of prove-driven responses. In either unit type, the
best IPD and IPD tuning width of (adapted) units were invariant with
the adapter IPD. This indicates that the psychophysical LA is not caused
by changes in IPD tuning of specific groups of neurons. Possibly, the
LA is a result of modulated distribution of activation across neural
Interaural Correlation Functions in the Inferior
Colliculus of the Guinea Pig
*Trevor M. Shackleton
, Robert H Arnott, Alan R. Palmer, Institute of
Hearing Research, Medical Research Council, Nottingham,
England NG7 2RD United Kingdom
Models of binaural hearing based upon interaural correlation account
for much of the human discrimination data and are consistent with the
responses of inferior colliculus (IC) cells to interaural time differences
(ITD) in tones and noise. However, there are few reports of direct
measurements of sensitivity of neurons to interaural correlation in
mammalian species. Interaural correlation versus spike count functions
(ICFs) from ñ1.0 to +1.0 (0.1 steps) were measured in low-frequency IC
cells of urethane anaesthetised guinea pigs at both zero and Best ITD
using broad-band (50 to 5000 Hz) and narrow-band (1 ERB around best
frequency), 50 ms long, noises at 20 dB above threshold. The noise was
resynthesized on each presentation and the sample correlation was used
in the ICF. The ICFs were classified as either linear, quadratic or ramp,
depending upon whether a straight line, 2nd order polynomial or
function comprising a constant section plus a sloping section best fit the
data. At zero ITD, linear ICFs were most common (26/47 narrow-band
noise, 13/26 broad) followed by quadratic (15/47 narrow, 11/47 broad).
At Best ITD, linear and quadratic ICFs were nearly equally common
(9/23 linear, 12/23 quadratic, pooled bandwidths). Ramp type ICFs
were uncommon for both zero (6/47 narrow, 2/26 broad) and Best
(2/23) ITD. Analyses of single-cell interaural correlation discrimination
were difficult because of high variability in the data, but discrimination
thresholds obtained were at least at least an order of magnitude greater
than human thresholds. Thus although single IC cells provide sufficient
information for discriminating the ITD of deterministic signals (i.e.
tones; Shackleton
et al.
ARO abstracts 24: 210) they do not for the
discrimination of interaural correlation of random signals.
Inhibition Sharpens Tuning to Interaural Time
Disparities (ITDs) in the Inferior Colliculus of the
Unanesthetized Rabbit
*S. J. Sterbing
, William R. D’Angelo
, Ernst-Michael Ostapoff
Douglas C Fitzpatrick
, Shigeyuki Kuwada
Dept. of
Neuroscience, UCONN Health Ctr., Farmington, CT 06030,
Otolaryngology and Head and Neck Surgery, University of
North Carolina at Chapel Hill, Chapel Hill, NC
A major cue for the localization of sound in space is ITDs. We
examined the role of inhibition in the sharpening of ITD tuning seen in
the inferior colliculus (IC) compared to the superior olivary complex.
Specifically, we examined the effects of GABA, a prominent inhibitory
transmitter, and bicuculline, a GABA antagonist, on IC neurons
sensitive to ITDs. The agents were iontophoretically injected through a
multi-barrel pipette while simultaneously recording from single IC
neurons. The effects on firing rate and ITD tuning were evaluated
before, during and after the application of the different drugs. If GABA-
mediated inhibition is involved in sharpening ITD tuning in IC neurons,
then applying additional amounts of this inhibitory transmitter should
further sharpen ITD tuning. Indeed, for almost all neurons tested,
GABA considerably sharpened the ITD functions and reduced the firing
rate. If inhibitory inputs serve to attenuate and sharpen the ITD
response, as suggested by our GABA experiments, blocking inhibitory
inputs with bicuculline should enhance the firing rate and broaden the
ITD response. As predicted, bicuculline often dramatically increased the
activity of IC neurons sensitive to ITDs and broadened their ITD tuning.
A major source of GABA-ergic input to the IC comes from the dorsal
nucleus of the lateral lemniscus (DNLL). Our preliminary experiments
indicate that inactivating the DNLL broadens the ITD tuning of IC
neurons on the opposite side.
Supported by NIDCD grants R01 DC02178-18 and T32 DC00025.
Sensorimotor Activity of Midbrain Neurons During
Head Orienting in Awake Barn Owls (Tyto alba)
*Anja Johnen
, Hermann Wagner, Bernhard H. Gaese, Institut f.
Biologie II, RWTH Aachen, Kopernikusstr. 16, Aachen, NRW
52072 Germany
The barn owl is a well established model for sound localization. In
response to faint sounds barn owls turn their head precisely towards the
direction of the sound source. A map of auditory space has been
described for the owl’s midbrain and was tested for behavioral relevance
using focal electrolytic lesions and direct electrical stimulation. These
studies showed that activation of midbrain neurons is sufficient to evoke

ARO Abstracts 14 Volume 25, 2002
head turnings towards contralateral directions. However, it remained
unclear if auditory neurons are separated from premotor neurons, thus
requiring auditory information to be relayed from sensory to premotor
parts of the optic tectum (OT).
Here we recorded extracellular activity from OT units of awake,
behaving barn owls. Owls performed a cue-directed selection paradigm
where a visual cue pointed towards the side of the next relevant auditory
target. Owls responded to auditory stimulation with a head turn towards
the sound source. Head orienting was measured with a magnetic
tracking system. We found that most neurons (71%) with auditory-
evoked activity also showed movement-related activation that depended
on the response side: Orienting towards contralateral directions was
paralleled by an increase in spike rate and orienting towards ipsilateral
directions by a decrease below spontaneous levels. A similar but less
explicit activation pattern was found before movement onset,
suggesting an influence of spatial attention. These results show that OT
units act as sensorimotor interface neurons and that they are possibly
also involved in the control of non-reflexive orienting behavior.
Supported by the DFG (SPP 1001 “Sensomotorische Integration”)
Effects of SPL on Sensitivity to Interaural Intensity
Differences in the LSO and IC
*Thomas J Park
, Achim Klug
, Benedikt Grothe
Sciences, Univ of Ill at Chicago, 840 W. Taylor St., Chicago, IL
Vollum Inst, Oregon Health Sci U, Portland, OR,
Auditory Physiology, Max-Planck-Institute of Neurobiology,
Am Klopferspitz 18a, Martinsried, Bavaria D-82152 Germany
The lateral superior olive (LSO) is dominated by neurons that are
sensitive to interaural intensity differences (IIDs), in that they respond
maximally to a particular range of IIDs. However, the responses of LSO
cells are also influenced by other stimulus parameters such as
frequency, duration, and overall intensity. The present investigation was
aimed at assessing the influence of overall intensity on IID sensitivity in
the LSO, and for comparison in the inferior colliculus (IC), which
receives a strong projection from the LSO, and has many IID-sensitive
cells. We recorded from single cells in the free-tailed bat, that were
predominantly excited by stimulation of one ear, and predominantly
inhibited by stimulation of the other ear (EI type). We generated IID
functions by holding the intensity to the excitatory ear constant and
varying the intensity to the inhibitory ear. We assessed the effects of
overall intensity by taking 3 or more functions at different excitatory
intensities, and quantifying changes in the 50% points of the functions.
We found that the IID sensitivity of the majority of cells in both nuclei
was greatly affected by overall intensity. However, the effects were
much more profound in LSO, for both magnitude of effects, and for
number of cells affected (LSO 94%, IC 68%). Also, LSO and IC cells
showed different types of effects. The majority of LSO cells showed a
systematic shift in sensitivity: at higher overall intensities, a greater
relative intensity at the excitatory ear compared to the inhibitory ear
was observed at the 50% points of the IID functions. Only 20% of the
IC cells showed this type of pattern, with 44% showing non-systematic
shifts. Finally, despite high variability among individual cells, a
population analysis of the proportions of cells responding to various
IID/overall intensity combinations showed a surprisingly invariant IID
sensitivity across overall intensities, and invariance was greater in the
IC than the LSO.
Localization in the anechoic environment and with
virtual acoustical directional presentation investigated with a
laser-pointing method
*Bernhard U. Seeber
, AG Technische Akustik, MMK, Munich Univ. of
Technology, Arcisstr. 21, Munich, BY D-80290 Germany
Many scientific studies investigate the acoustical localization in the
field of vision. Hence it is suitable to display the perceived auditory
direction by a light point. In formerly known methods subjects use a
hand-held light pointer or a pivoted pointer in front of them. However,
the subject’s motor system or the optical parallax may influence the
results of those techniques. Instead, the newly proposed method utilizes
a laser pointer with a deflection unit. Subjects enter the perceived
direction with a trackball. The laser spot moves according to the
rotation of the ball smoothly on a defined track. Localization results
obtained by this method are presented. The reproduction of the
acoustical direction was varied in three ways: free-field, headphones
using individual HRTFs, and headphones using selected non-individual
HRTFs. Furthermore, the influence of the initial laser spot position is
investigated. The intuitive experimental operation and the high
resolution of the laser-pointer method make it particularly suitable for
localization research in audiology, psychoacoustics, and virtual
Effect of Cuing on Sound Localization Accuracy in a
*Norbert Kopco
, Barbara G. Shinn-Cunningham
Hearing Research
Center and Cognitive and Neural Systems Dept., Boston
University, 677 Beacon St., Boston, MA 02215,
Research Center, Departments of Cognitive and Neural Systems
and Biomedical Engineering, Boston University, 677 Beacon
Street, Boston, MA 02215
A previous study of auditory attention examined how auditory
localization accuracy in an ordinary room is affected when a test
stimulus is preceded by an auditory cue from either the correct or
opposite hemifield (Kopco, Ler, and Shinn-Cunningham, JASA, 109,
2377). Results suggested that the auditory cue does not improve
localization accuracy, even when the cue is always informative. In fact,
the presence of a preceding cue from either +90 or
ñ90 degrees azimuth
caused a consistent localization bias of the test stimulus (causing the
test stimulus to be heard more towards the midline) for cue-test delays
as long as 300 ms. In the current study, these findings are extended to
determine how the azimuthal position of the cue stimulus affects
localization bias. Acoustic analysis examines the extent to which
localization bias can be explained by the reverberation in the room
(which has a broadband T
of roughly 450 ms), as opposed to
perceptual effects (e.g., Carlile, Hyams, and Delaney, JASA 110, 416-
[Work supported in part by AFOSR Grant No. F49620-01-1-0005 and
the Alfred P. Sloan Foundation]
Do Up/Down Reversals Really Exist?
*Geoff Eberle
, Ken I McAnally
, Russell L Martin
Deakin University, Waurn Ponds, Geelong, Victoria 3217
Air Operations Division, Defence Science and
Technology Organisation, Melbourne, Victoria Australia
Interaural time and intensity cues are sufficient to specify a cone-of-
confusion upon which a sound source may lie. The cone-of-confusion is
thought to be resolved by spectral cues to sound-source elevation and
front/back hemifield. The literature reports instances of front/back
confusion, where a localisation response is in the wrong front/back
hemifield. Presumably, these confusions arise when the cue to
front/back hemifield is unreliable. Less frequently reported are
instances of up/down confusion (where a localisation response is in the
wrong up/down hemifield). We sought statistical evidence for
localisation ëreversalsí, which are a type of confusion for which the true
and perceived sound-source locations are symmetrical about the mid-
frontal or mid-transverse plane. Up/down reversals suggest the
availability of a cue to sound-source angle, in any direction, relative to
straight ahead. Localisation response distributions, for a free-field
localisation task, were analysed using mixture distribution techniques.
A significant bimodal distribution across the front/back or up/down
dimension with the two modes located symmetrically was taken as
statistical evidence for localisation reversals. Not surprisingly, statistical
evidence was found for front/back reversals. However, little evidence
was found for up/down reversals. It was thought that this may be due to

ARO Abstracts 15 Volume 25, 2002
the presence of a robust cue to up/down hemifield, possibly provided by
the torso. A follow-up experiment using virtual-audio techniques was
also conducted. The HRTFs for that experiment were measured with the
head oriented directly up, causing any spectral influence of the torso to
be symmetrical about the mid-transverse plane of the head. Again little
evidence was found for up/down reversals.
Behavioral Performance in Binaural Tasks is
Determined by Membrane Kinetics of Binaural Coincidence
*Torsten Marquardt
, David McAlpin, Department of Physiology,
Univerity College London, London, England WC1E 6BT United
Phase-locked spike input to binaural coincidence-detector neurons in
the superior olivary complex (SOC) underpins their physiological
sensitivity to interaural time differences (ITDs). However, simulation of
SOC neuron responses to ITDs, using a modified Hodgkin-Huxley
model (Rothman et al., 1993, J. Neurophysiol. 70, 2562ff), reveals the
dependence on stimulus frequency of ITD sensitivity to be different to
the monotonic decrease in phase-locking with stimulus frequency, and
its pronounced cut-off above 1 kHz (Johnson, 1980, J. Acoust. Soc.
Am. 68, 1115ff). The simulations show a clear maximum of ITD-
sensitivity, as determined by the extent to which their response is
modulation with ITD, at signal frequencies around 350 Hz. This is in
agreement with the frequency region over which the binaural masking
level difference (BMLD) is maximal (Durlach and Colburn, 1978, in:
Handbook of Perception. Vol. IV, fig. 50). The BMLD is a
psychophysical phenomenon which is presumed to be directly related to
ITD-sensitivity of such neurons. Further analysis of the simulations
indicates that ITD sensitivity depends not only on phase-locking but to
a substantial extent on the membrane kinetics of SOC neurons. A
commonly asked question is why the frequency regions for maximum
BMLD (350 Hz) and best ITD discrimination (approx. 800 Hz, see
Durlach and Colburn, 1978, fig. 39) differ. When lateralisation is
explained in terms of the balance between two spatially-tuned
channels, as suggested by McAlpine et al. (Nature Neurosci. 4, 396ff),
then the slopes of both overlapping channels determine ITD
discrimination ability. With increasing frequency, the shorter
periodicity of the auto-correlation function counteracts the decrease in
steepness of these slopes as a result of decreasing ITD-sensitivity.
Consequently, the frequency for which slopes of ITD functions are
steepest (ITD discrimination) is above the frequency of maximum ITD
sensitivity (BMLD maximum).
Supported by the MRC
Comparison of Relative and Absolute Measures of
Sound Localization in Cats Obtained Under Identical
Acoustic Conditions.
*Jordan Moore
, Daniel J Tollin, Tom C.T. Yin, Department of
Physiology, University of Wisconsin, 1300 University Ave,
Madison, WI 53706
Studies of localization use relative or absolute psychophysical
paradigms. Relative tasks assess acuity by determining the smallest
angle separating two sources, the minimum audible angle (MAA), that
can be discriminated. The MAA varies with stimulus frequency,
duration, level, and location. Absolute tasks measure the actual ability
to indicate sound location. Changing stimulus parameters affects the
accuracy and precision of the location estimates. But whether and how
these two measures are related and whether or not the same neural
mechanisms mediate performance on these two tasks is unknown. Here,
we examine the relationship between absolute and relative measures of
localization in cats. Cats were trained using operant conditioning to
make orienting gaze shifts (combined eye and head movements) to
acoustic targets from an initial fixation LED. Independent variables
were the angle (horizontal or vertical) between the fixation LED and the
source and the properties of the stimuli. Stimuli consisted of broadband
noises (15ms-1sec durations), high- and low-pass noise, and 1/6 octave
narrowband noise. The data were separated into two groups based on
trial number. Data from one group were analyzed as an absolute task
and measures of precision and accuracy of the final gaze were
determined. The remaining data were analyzed as a relative task and
only the initial direction of gaze, and not magnitude, was used to
determine the percentage of ìcorrectî shifts toward the target; gazes
away and non-responses were considered ìincorrectî responses. This
method is similar to that used in infant localization studies. The MAA
was computed using the bias-free measure, d’. In general, horizontal
MAAs were smaller than vertical MAAs mirroring the smaller standard
deviations of absolute localization estimates for horizontal than vertical
targets. But the MAAs were larger than the corresponding standard
deviations of the actual location estimates.
Support: NIH DC00116, DC02840, DC00376
The Headaim of Echolocating Bats Tracking Moving
and Stationary Prey
*Kaushik Ghose
, Cynthia F. Moss, Department of Psychology,
University of Maryland, Biology/Psychology Building, 4102C,
College Park, MD 20742
A long-standing question of interest to bat researchers is whether
echolocating bats employ any predictive strategy when tracking moving
prey. A predictive strategy would be revealed by orienting movements
that are not simply directed towards the last known target position but
use some information from previous echoes to anticipate a new target
location. Another issue concerns the orienting behavior of the bat before
and after detecting a target.
Here we study these questions by measuring the sonar beam pattern of
flying echolocating bats (Eptesicus fuscus) as they attack tethered insect
prey in a flightroom. Sixteen microphones arranged in a planar ‘c’
shaped array were used to measure sonar beam patterns. Head aim of
the bats was inferred from the beampattern and used as an index of
orienting behavior. Two high-speed infrared digital cameras recorded
the bat’s flight behavior and other relevant objects in the room. The bat’s
flight path and positions of any targets were reconstructed from the
Trials where bats attacked moving prey were studied to check for any
predictive strategy being used. Specifically, the sonar beam aim [head
aim] for each vocalization was analyzed and compared with the actual
target location at that instant. In some trials, tethered prey was dropped
into the flight space while the bat was searching. The time course of
orientation to the prey and the accuracy of orientation over successive
vocalizations was measured.
Supported by NSF and Whitehall grants to CFM
Echolocation Behavior of Free-flying FM-bats Taking
Tethered Insects in a Cluttered Environment.
*Cynthia F. Moss
, Kari A. Bohn
, Hannah Gilkenson
, Annemarie
Department of Psychology, University of Maryland,
College Park, MD 20742,
Department of Biology, Odense
University, Campusvej 55, DK-5230 Odense, DK-5230 Denmark
The FM-bat,
Eptesicus fuscus
, uses sonar to detect, localize, track and
intercept insect prey on the wing. While this species is generally
considered an open-space forager, recent reports indicate that
E. fuscus
also captures insects near clutter (Simmons et al., JARO, 2001),
suggesting a wider repertoire of sonar-guided behavior than previously
documented. Here, we present lab studies of insect capture behavior by
E. fuscus
and detail their adaptations in flight behavior and sonar
vocalizations in the presence of vegetation clutter.
Bats were trained to capture tethered mealworms in a flight room lined
with acoustic foam. Their behaviors were studied under open-room and
clutter conditions. In clutter, the tethered insect was suspended 5-40 cm
from leafy houseplants. Experiments were carried out using only long
wavelength lighting to preclude the use of vision. Two gen-locked,

ARO Abstracts 16 Volume 25, 2002
high-speed video cameras (240 Hz) recorded target position, bat flight
path, and capture behavior. The resulting images were used to calculate
the 3-D positions of the bat, target, and clutter. The bat’s sonar cries
were recorded with ultrasound microphones and digitized at 250 kHz
over a time period that corresponded precisely to the video segment for
a given trial.
With experience foraging in a cluttered environment,
E. fuscus
their echolocation behaviors to successfully intercept insect prey
positioned as close as 10 cm from vegetation. Beginning approximately
700 ms prior to insect capture and continuing for 300 ms after capture
in clutter, bats produced groups of sounds with stable IPI, interrupted by
longer intervals. Changes in the temporal patterning, bandwidth and
duration of the bat’s sonar signals accompanied acquisition of this task
over a period of several days.
A Neural Network Sound Localization Model of
Echolocating Bat, Eptesicus fuscus.
*Murat Aytekin
, Cynthia F. Moss, Department of Psychology,
University of Maryland, College Park, MD 20742
, an echolocating bat, uses short duration (1ms-10ms)
frequency modulated (FM) ultrasonic calls during the approach and
terminal phases of insect pursuit and monitors the 3-D positions of
objects in the environment from the acoustic information in returning
echoes. Acoustic transformation of echoes by external ears, head, wings
and torso at the ear canal can be mathematically described as directional
transfer functions (DTF). DTFs provide unique cues for sound location,
enabling a representation of the bats 3-D auditory scene.
It is widely accepted that interaural level differences (ILD) for bats are
good indicators of sound source location in azimuth, whereas, cues for
elevation are embedded in the monaural spectral structure of the DTFs.
However, it is not known how these cues may be combined in the batís
sonar receiver to represent the locations of objects in 3-D space. A
biologically plausible neural network model is a useful approach to
investigate the available localization information without any constraint
on the cues, thus providing new insights to bat sound localization.
We measured DTFs across 545 different positions, spanning whole
frontal hemisphere from 4 different bat preparations. Ears were
preserved in their natural position and the wings extended to the sides in
a flight posture. 1mm diameter microphones were implanted at the
position of the tympanic membrane. We are employing a time delay
neural network (TDNN) for sound localization. DTFís and a cochlear
model provide the inputs to the TDNN. Using the TDNN to extract the
available localization information from its inputs, we are studying the
effects of the sonar target position and signal characteristics (e.g.
bandwidth, sweep rate) on model localization performance.
Supported by NIMH and Whitehall awards to CFM.
Discrimination of azimuth in a forced-choice test is
dependent on direction of sound incidence in a small
passerine bird
*Brian S. Nelson
, Roderick A. Suthers
Department of Biology,
Indiana University, Jordan Hall 142, 1001 E. 3rd Street,
Bloomington, IN 47405,
Medical Sciences Program, Indiana
University, Bloomington, IN
Laboratory experiments have often demonstrated that small birds are
unremarkable in their sound localization abilities. In addition, small
head size appears to limit interaural time and intensity differences (ITD
and IID) available over biologically relevant sound frequencies. Despite
these observations and apparent physical limitations, eastern towhees,
Pipilo erythrophthalmus, (Emberizidae, Passeriformes) assess azimuth
with surprising accuracy in natural habitat. To better understand this
discrepancy, and obtain insights into sound localization mechanisms
employed by small birds, we have begun conducting 2-alternative
forced choice (2AFC) tests with eastern towhees in both the laboratory
and in an outside aviary. Towhees in these tests can discriminate
azimuth nearly as well as in the field (to within 10∞), however,
performance in tests described is highly dependent on head orientation
(direction of sound incidence). Results suggest that interaural
differences (ITD or IID) do not vary monotonically with direction of
sound incidence. Instead, results suggest that interaural differences may
oscillate asymmetrically as a function of azimuth within each lateral
hemifield. We propose that towhees employ sound localization
mechanisms that operate efficiently over long distances in natural
Supported by NSF grant BIR-9413220 and NIH grant NS-29467.
Spatial unmasking of speech in simulated anechoic and
reverberant rooms
*Barbara G. Shinn-Cunningham
, Scarlet Constant
, Norbert Kopco
Hearing Research Center, Departments of Cognitive and Neural
Systems and Biomedical Engineering, Boston University, 677
Beacon Street, Boston, MA 02215,
Medical Science, Boston
University, Boston, 02215 ,
Hearing Research Center,
Department of Cognitive and Neural Systems, Boston University,
Boston, 02215
Masked speech reception thresholds were measured for a speech source
in the presence of a speech-shaped noise masker for simulated anechoic
and reverberant listening conditions. Both speech and masker sources
were simulated using individualized HRTFs. The HRTFs were
measured in a moderately reverberant room (T
=450 ms) for sources at
different distances (15, 100, and 200 cm) and directions (straight ahead
and directly to the right of the subject). Reverberant simulations were
generated using the full HRTFs (including reverberation), while
anechoic simulations were generated by time windowing the full
HRTFs to create pseudo-anechoic HRTFs. Sp
eech and noise sources
were then convolved with the appropriate HRTFs to simulate anechoic
and reverberant simulations for different speech and noise
configurations. For each spatial configuration, subjects were tested
binaurally, monaurally with the ìbetterî ear, and monaurally with the
ìworseî ear. Speech reception thresholds were measured adaptively,
varying the target level while keeping the direct portion of the masker
constant at the better ear. Results suggest that speech intelligibility
improves and spatial unmasking increases when reverberation is
included, at least for some of the tested spatial configurations. However,
the binaural contribution to spatial unmasking is generally small and
tends to decrease when reverberation is included.
[Work supported in part by AFOSR Grant No. F49620-01-1-0005 and
the Alfred P. Sloan Foundation]
Investigations of the precedence effect in budgerigars
(Melopsittacus undulatus)
*Micheal L. Dent
, Robert J. Dooling, Department of Psychology,
University of Maryland, College Park, MD 20742
The precedence effect has previously been f
ound in mammals, anurans,
invertebrates, and one species of bird, the barn owl. Here, the
precedence effect was measured in a small parrot, the budgerigar
(Melopsittacus undulatus). The general hearing capabilities of
budgerigars have been well examined. While they have unremarkable
sound localization abilities, they do exhibit free-field binaural
unmasking at amounts similar to those found in humans with much
larger heads. Using operant conditioning procedures, we examined
whether budgerigars exhibited the pr
ecedence effect in a manner similar
to humans and other animals. Psychoacoustic methods were used to
measure discrimination performance of click pairs from different
locations in space and separated by a short delay, simulating a sound
source and its echo. Localization dominance was found at interstimulus
delays of 0.5 ms to 5.0 ms, where discrimination performance between
click pairs was high because the echoes were s
Discrimination performance was poor at shorter and longer
interstimulus delays, during summing localization and past the echo
thresholds. Further experiments showed that intensity differences

ARO Abstracts 17 Volume 25, 2002
between a lead-lag stimulus pair could override time differences
between the lead and lag, the timecourse of the aspects of the
precedence effect changed with the intensity and duration of the stimuli
but were not asymmetric with respect to leading stimulus location,
localization dominance could be built-up and broken down, localization
dominance occurred along the midline where minimal interaural time
difference cues were available, and two other species of small birds also
exhibited the aspects of the precedence effect. Most of these results are
similar to those found previously in other animals, suggesting that the
precedence effect is a general auditory mechanism for s
echoes in an animal’s environment.
Auditory Velocity Aftereffects with Varying Interaural
Time Differences
*Hisashi Uematsu
, Makio Kashino, Tatsuya Hirahara, Human &
Information Science Lab., NTT Communication Science Labs., 3-
1, Morinosato-Wakamiya, Atsugi, Kanagawa 243-0198 Japan
Following prolonged listening to an adapting sound moving across the
horizontal plane, a stationary test sound can be perceived as moving in
the opposite direction, the effect known as the auditory motion
aftereffect. Here we report another effect of adaptation to a moving
sound, that is, changes in perceived velocity of a moving test sound,
named auditory velocity aftereffect. Apparent sound movement was
produced by varying only interaural time differences (ITDs). The
subjective velocity of a test sound was measured using the constant
method with a two-alternative forced-choice paradigm. In
each trial, an
adapting tone (500 Hz, approximately 10 s) was presented first,
followed by a test tone (500 Hz, 1 s) and then a standard tone (250 Hz,
1 s), with 100-ms silent intervals between them. The frequency of the
standard tone was chosen because our previous study indicated that
frequency separation of an octave is enough to prevent the motion
aftereffect. Subjects were requested to judge whether the test tone or the
standard tone was perceived as moving faster. The velocity (i.e., ITD
change rate) of the adapting tone was selected from eight values
between 100 μs/s and 3600 μs/s and fixed through a session. The
velocity of the test tone was selected randomly from seven values
between 200 μs/s and 900 μs/s on
each trial, and that of the standard
tone was fixed throughout a session either at 300 μs/s or 700 μs/s.
Psychometric functions were estimated using the maximum likelihood
method. A test tone was found to be perceived as moving slower than
the veridical value due to adaptation, and the largest aftereffect was
observed when the velocity of the test tone was slightly slower than that
of the adapting tone. These findings put constraints on models of
auditory motion perception.
Stochastic Signals and the Franssen Effect
*William M Whitmer
, Stanley E. Sheft, Christopher A Brown, Parmly
Hearing Institute, Loyola University Chicago, 6525 N. Sheridan
Rd., B9 DH, Chicago, IL 60626
The Franssen effect, the identification and localization of steady-state
(slow onset) sounds as being the same as simultaneous transient (sudden
onset) sounds, has been previously thought to be limited to pure tones in
reverberant rooms. To examine the role of random signal variations
(noise) in the Franssen effect, listeners heard transient/steady-state
signal pairs from either one or two loudspeakers in a six-speaker array.
Stimuli were Gaussian narrow-band noises with 2-4096 Hz bandwidths,
centered at 250, 1000 and 4000 Hz. Initial transient RMS level was
within 3 dB of maximum level. The breakdown of the Franssen effect -
- perceiving the steady-state sound at its actual location — did not occur
for 1000-Hz-centered signals until the bandwidth was greater than 128
Hz, yet the steady-state portions of these signals were localizable.
Responses to regular envelope fluctuations (sinusoidally amplitude
modulated pure tones with equivalent bandwidths) did not exhibit the
same breakdown of the effect as stochastic fluctuations. Room
responses to narrow-band signals were analyzed; binaural cross-
correlations showed little indication of the effect. Mannequin
recordings of narrow-band stimuli in the same enclosure, presented to
listeners over headphones, yielded similar responses. Results suggest
that the Franssen effect is not wholly dependent on the localizability of
the steady-state signal.
Work supported by NIDCD.
Phonemic Contrasts in a Multiple-Talker Task with
Normal Hearing and Sensorineural Hearing Loss
*Pamela Jean Mishler
, Mark A Ericson
, Shawn Cowell
Department (126), Dayton Veterans AffairsMedical Center, 4100
West Third Street, Dayton, OH 45428,
AFRL, WPAFB, Dayton,
Individuals with sensorineural hearing loss (SNHL) have difficulty
understanding sp
eech in adverse listening environments. Past studies
have shown the effects of hearing loss and spatial separation on speech
intelligibility. However, little is known about specific phonemic losses
in speech intelligibility due to the combination of hearing impairment
and spatial separation. The purpose of this study was to measure word
identification ability of normal hearing and hearing-impaired
individuals in a multi-talker task. Thirty-three listeners in each group
participated in each test condition. The hearing-impaired listeners were
below 60 years in age and exhibited a high frequency, cochlear hearing
loss. The normal hearing listeners were age-matched to the hearing-
impaired group. Recordings of the Modified Rhyme Test (MRT) were
made with six male and six female talkers. The speech files were
digitized and edited to time-align the test words and equalize sound
levels. Multiple phrases from the MRT were processed through a TDT
Power-DAC with non-individualized head related transfer functions and
presented over Sennheisser HD600 headphones. The MRT phrases
were presented at 0 dB SNR with and without spatial separation. The
independent variables included two age-matched, equal size groups of
normal hearing and SNHL listeners. The dependent variable was the
phonemic contrasts within the word identification responses. Analysis
of the data revealed a main effect for hearing loss and spatial separation.
A difference in the type of phonemic contrasts between the two groups
was found, especially for phonemes with high frequency content.
Work sponsored by Veterans Affairs VISN10 RI program.
Information Theoretical Analysis of Spike Count and
Latency Codes for Acoustic Space in Primary Cortical
*Jan WH Schnupp
, Israel Nelken
, Tom D Mrsic-Flogel
, Andrew J.
Physiology Dept., University of Oxford, Oxford, United
Physiology, Hebrew University, Jerusalem, Israel
When tested with brief noise bursts presented in virtual acoustic space,
most A1 neurons will respond with brief “onset” bursts of action
potentials. Brugge and colleagues (J Neurosci, 1996; 16: 4420-37) have
proposed that A1 neurons may signal source position through variations
in the timing (latency) of these onset responses, rather than through
variations in spike count. However, it has been observed in a number of
sensory systems that response strength and response latency may show
a systematic relationship (stronger responses in terms of discharge rate
tend to occur with shorter onset latencies). This relationship may arise
naturally from the manner in which synaptic potentials are integrated
within neurons. Consequently, response latency and spike count codes
might be manifestations of the same underlying signalling mechanisms.
When we applied an information theoretical analysis to the presumed
spike count and spike latency codes, we found the amount of
information transmitted through either of the candidate codes to
correlate highly, but the amount of information transmitted by latency
was in most cases slightly higher than that transmitted by spike count.
We also found the two candidate codes to be highly redundant, in that
little extra information could be gained by observing both spike count
and latency over that obtained by observing only one of these variables
alone. The high redundancy of the spike count and latency codes seems
to support the notion that both these codes may be largely due to a

ARO Abstracts 18 Volume 25, 2002
common encoding mechanism, but it seems likely that additional
mechanisms must contribute to the the higher amount of information
observed in response latency.
A Psychophysical Group Study of Developmental Tune-
*Jennifer Louise Dean
, Jessica M Foxton
, Ani Patel
, Isabelle Peretz
Timothy D Griffiths
Department of Physiological Sciences,
Newcastle University Medical School, Framlington Place,
Newcastle upon Tyne, NE2 4HH United Kingdom,
Neurobiology, The Neurosciences Institute, San Diego,
DÈpartment de Psychologie, UniversitÈ de MontrÈal, MontrÈal,
Disorders of musical perception in the absence of deafness or brain
condition have been described (Allen, 1878, Mind: 10, 157-167). Early
descriptive studies describe deficits in pitch discrimination, tonal
memory, and singing. We present a systematic assessment of such a
tune-deaf sample.
Six subjects (2 male, 4 female: aged 35-56) described lifelong
inabilities to perceive music. Pure tone audiograms and auditory filter
widths (notched-noise method) were normal. Complex sound perception
was assessed using a validated 2-AFC test battery (Griffiths et al, 2001,
Hear Res: 154, 165-169). Estimated thresholds were determined from a
Weibull fit to full psychometric function and compared with 17 age-
matched controls. Perception of sinusoidal frequency modulation of a
500Hz carrier was normal for all subjects at 2Hz, but not at 40Hz and
120Hz. Perception of sinusoidal amplitude modulation of a 500Hz
carrier was impaired for some subjects at 2Hz, 40Hz, and 120Hz.
Within- and between-channel gap detection was normal for all subjects
(excluding one). The threshold for the detection of regular interval noise
was normal for all subjects (excluding one). Impairments were
demonstrated for selective subtests of a validated musical test battery,
(Liegeois-Chauvel et al, 1998, Brain: 121, 1853-1867). Prosody
perception (Patel et al, 1998, Brain Lang, 61: 123-144) was normal for
all subjects.
The findings support the existence of a developmental disorder of
musical perception in the absence of peripheral deafness or neurological
event. We show, further, that the disorder is associated with deficits in
the perception of patterned sound.
Effect of Listening Experience on the Perception of
Periodicity Strength in Chinchillas
*William P. Shofner
, Parmly Hearing Institute, Loyola University
Chicago, 6525 North Sheridan Road, Chicago, IL 60626
In stimulus generalization tasks, an animal is trained to respond to a
particular stimulus, and responses are then measured to test stimuli that
vary systematically along a stimulus dimension. A gradient in
behavioral responses (1) suggests how closely test stimuli are perceived
by the animal to resemble the training stimulus, (2) is consistent with
the hypothesis that the animal possesses a perceptual dimension related
to the stimulus dimension, and (3) can indicate what stimulus features
are being analyzed during testing. Chinchillas trained to discriminate a
cosine-phase harmonic tone complex (COS) from wideband noise
(WBN) were tested in a generalization task with COS, random-phase
complex tones (RND) and iterated rippled noises (IRNs). Preliminary
generalization data indicated that chinchillas order complex sounds
along a dimension related to stimulus periodicity strength (Shofner,
2001, JASA 109: 2465). Data from naive chinchillas suggested that the
stimulus envelope had a large influence on the perception of periodicity
strength, but data from one animal having previous listening experience
with IRN indicated that the fine structure had a larger influence than
envelope on this perception. To examine the effect of listening
experience with IRN on the perception of periodicity strength, 3 of the
above naive animals were retrained to discriminate IRN from WBN and
were tested in the generalization task with IRNs, COS, and RND.
Retrained animals now gave larger behavioral responses to test stimuli
having small envelope periodicity strengths (i.e. RND, IRNs) than given
previously in the naive condition. The results suggest that for broadband
stimuli comprised of resolved and unresolved components, the
chinchilla may normally analyze periodicity information in the stimulus
envelope, but can learn to analyze information in the fine structure
when trained with a stimulus having a small envelope periodicity
Supported by NIDCD P01 DC00293
Interaction between envelope and carrier periodicity in
tonal noises
*Alexandra Stein
, Lutz Wiegrebe, Abt. Prof. Neuweiler, Zoologisches
Institut Der LMU, Luisenstr. 14, 80333 Munchen, Bavaria
Psychoacoustic models for pitch detection and models for modulation
detection are currently developing independently from one another.
Does this dichotomy in psychoacoustic modeling reflect the existence
of two independent subsystems for pitch and modulation processing?
Modulated noises can also produce a tonal sensation and tonality is
generally produced by the periodicity of the stimulus. To approach the
idea of a common mechanism for periodicity detection, this study
evaluates the extent of perceptual interaction between envelope and
carrier periodicity. Envelope periodicity can be obtained by multiplying
Gaussian Noise (GN) with a sinusoidal modulator. Carrier periodicity
can be obtained by iterating a delay-and-add processing of GN, which
generates Iterated Rippled Noise (IRN). Since IRN has a distinct pitch
and does not show pronounced modulation in the envelope, it is
particularly suitable to represent carrier periodicity in this study. To
study the mutual influence of envelope and carrier periodicity, two sets
of experiments were designed. One set dealt with the ability to detect
envelope periodicity in absence and in presence of carrier periodicity. In
the counter experiments, the listeners’ task was to detect carrier
periodicity in absence and in presence of envelope periodicity. The
period of the modulator and the period of the corresponding carrier
were always set to be the same. The results show that the sensitivity for
envelope periodicity is significantly reduced in the presence of carrier
periodicity, independent of the modulation period. However, the
sensitivity for carrier periodicity is affected by the presence of envelope
periodicity only for frequencies below about 50 Hz. Existing pitch and
modulation models are tested, whether they can reproduce the results
obtained in these psychoacoustic experiments.
The Role of Harmonic Resolution in Diotic and
Dichotic Pitch Perception
*Joshua Gary Bernstein
, Andrew John Oxenham
Speech and
Hearing Sciences Program, Harvard-MIT Division of Health
Sciences and Technology, 77 Massachusetts Avenue, Cambridge,
MA 02139,
Research Lab of Electronics, Massachusetts Institute
of Technology, 77 Massachusetts Avenue, Cambridge, MA
Two experiments investigated the relationship between the pitch
salience of harmonic complexes and the resolvability of individual
components. In
each experiment, tone complexes with 12 successive
equal-amplitude random-phase harmonic components of a 100- or 200-
Hz fundamental frequency (F
) were presented dichotically or
diotically, for a total of four conditions. Under dichotic presentation,
even and odd harmonics were presented to opposite ears, such that the
peripheral spacing between components was 2F
. Under diotic
presentation, all harmonics were presented to both ears, such that the
peripheral spacing was F
. The first experiment tested the resolvability
of individual harmonics, by measuring listenersí performance in
identifying whether a pure tone probe was higher or lower in frequency
than the target harmonic of the complex, made perceptually more
prominent by gating it on and off. Preliminary results indicate that
approximately the first 10 and 20 harmonics are resolvable in the diotic
and dichotic conditions, respectively, verifying that frequency

ARO Abstracts 19 Volume 25, 2002
selectivity is limited only peripherally. The second experiment
measured F
difference limens (DLs) as a function of lowest harmonic
number. In all four conditions, F
DLs increased dramatically as the
lowest harmonic number was increased from 9 to 15. The similarity of
the results at both F0s provides further evidence that harmonic number,
not absolute frequency, underlies the dramatic DL shift. The similarity
of the results under diotic and dichotic conditions indicates that the
auditory system, in performing F
discrimination, is unable to use the
information provided by the additional resolved harmonics in the
dichotic case. This result is consistent with a harmonic template theory
of pitch, in which only harmonics that are normally resolved contribute
in the calculation of pitch.
Supported by NIH Grants 5T32 DC 00038 and R01 DC 03909
A Systematic Clinical Battery for the Investigation of
Pitch Sequence Processing
*Jessica M Foxton
, Will Woods
, Tim D Griffiths
Department of
Physiological Sciences, Newcastle University Medical School,
Framlington Place, Newcastle
upon Tyne, Tyne and Wear NE2
4HH United Kingdom,
Physiology, Newcastle University,
Newcastle, Tyne and Wear, UK
We describe a systematic battery of tests for the assessment of pitch
sequence processing. Functional imaging demonstrates that such
processing involves cortical mechanisms beyond the primary auditory
cortex. Research into the neural bases of sequence processing and
music has uncovered dissociations between encoding the pitch interval
sizes in a musical sequence, called ëlocalí processing, and extracting the
pattern of rises and falls in pitch from note to note, often called
ëcontourí or ëglobalí processing (eg. Peretz, 1990). Here we suggest
that a level of pitch sequence processing has been overlooked in these
studies that represents a more ëglobalí level of auditory processing.
This hypothesised level enables the extraction of any overall pattern in
pitch, irrespective of the note-to-note pitch changes.
We present tests that assess processing at these three hypothesised
levels and have the potential to unearth dissociations between them. At
the first two levels the tests extend previous studies by Dowling to an
atonal scale (Dowling, 1978). At the third level we introduce a new test
that requires a same-different judgement on the overall pattern in pairs
of six-element pitch sequences. These sequences are atonal and
transposed in pitch between pairs. The overall pattern of the sequences
is determined by a power spectrum (p) of the form, p = frequency
The phase of each frequency com
ponent is randomised between
sequences, except for the lowest frequency component, where the phase
is either kept the same or inverted. This produces sequences with the
same or different overall pattern, irrespective of the note-to-note pitch
changes. This task can be accomplished by normal volunteers after a
short period of training and is realistic for clinical use.
Effects of Masker Phase Curvature for On- and Off-
frequency Simultaneous and Nonsimultaneous Maskers
*Stephan Ewert
, Andrew John Oxenham
Medizinische Physik,
Universit‰t Oldenburg, Oldenburg, Germany,
Research Lab of
Electronics, Massachusetts Institute of Technology, 77
Massachusetts Avenue, Cambridge, MA 02139
Repeating linear frequency sweeps (Schroeder phase stimuli) have been
used previously to estimate the phase curvature of the auditory filters.
As these harmonic stimuli have a constant phase curvature, one implicit
assumption is that the curvature of the auditory filters can be
approximated as being constant. Physiological measurements in
various mammals have shown that the assumption of constant phase
curvature is reasonable for frequencies within the passband of the
auditory filter, but not for frequencies well below the center frequency
(CF) of the filter. To investigate whether a similar change in phase
curvature with frequency can be found behaviorally in humans,
thresholds for a 2-kHz sinusoidal signal were measured in the presence
of simultaneous harmonic tone complex maskers with cutoff
frequencies of 1400 and 2600 Hz (on-frequency masker) or 200 and
1400 Hz (off-frequency masker). The phase curvature of the maskers
was varied systematically to find the curvature that produced the
minimum amount of masking. For the on-frequency masker, minimum
masking occurred at a positive curvature, consistent with previous
results. For the off-frequency masker, minimum masking occurred
around zero curvature. This suggests that the response to frequencies
well below CF exhibits no phase curvature, consistent with
physiological data. The maskers producing the highest and lowest
thresholds were selected from both the on- and off-frequency conditions
and were used as forward maskers. For the on-frequency masker, large
differences in threshold were apparent in forward masking also. For the
off-frequency maskers, the difference was greatly reduced. This is
qualitatively consistent with the expected effects of peripheral
nonlinearity on forward masking.
[Supported by NIH Grant R01 DC 03909.]
The Auditory Temporal Window in 9-10 Year Old
Children, Adults and Dyslexic Adults
*Penny Hill
, David Robert Moore, The University Laboratory of
Physiology, Oxford University, Parks Road, Oxford, Oxfordshire
OX1 3PT United Kingdom
It has been suggested that both young, normally developing children
and older people with language impairment have poor temporal
resolution – the ability to separate sounds in time. Work from this
laboratory (Hartley and Moore, ARO, 2002) has offered an alternative
interpretation, that poor processing efficiency in these groups leads to a
wider variety of auditory impairments. This study examined these
competing hypotheses by measuring the shape of the auditory temporal
window, the time during which sounds are integrated (Moore et al,
JASA, 83, 1102). Our experiments measured the rising arm of the
temporal window using backward masking with variable delays
between a target tone and a masking noise. Tone thresholds were
estimated for 9 dyslexic and 12 control adults, and 12 children (9-10
y.o.), all untrained and audiometrically normal, using a two AFC task.
Tone (1000Hz, 20ms including 10ms rise/fall) offsets occurred with a
delay of 0, 10, 50 and 150ms before the onset of a noise masker
(centred at 1000Hz, bandwidth 800Hz, 300ms). Presentation was
monaural over headphones to the right ear. The children experienced
more masking at every delay relative to the adults. This was greatest at
the shorter delays (0ms = 15dB, 10ms = 16dB, 50ms = 7dB, 150ms =
5dB) and the shape of the curve was flatter than the control adults. This
suggests a developmental change in the shape of the temporal window.
The generally elevated masking seen in the children relative to the
adults also suggests that there is a contribution from poor efficiency.
The dyslexic adults also had elevated masking, but this was less marked
than that in the children. However, the shape of the slope in the dyslexic
adults resembled that of the children. This may indicate that temporal
processing in adult dyslexics does not develop normally, and that both
poor temporal resolution and poor efficiency may contribute.
Excessive Auditory Masking in Children with
Language or Listening Impairments Interpreted as a
Developmental Delay
*Beverly Ann Wright
, Miriam D. Reid
Communication Sciences and
Disorders, Northwestern University, 2299 North Campus Drive,
Evanston, Illinois 60208-3550,
Otolaryngology, University of
California San Francisco, San Francisco, CA
Eight percent of children have language or listening disorders. Affected
children frequently have particular difficulty perceiving sounds in noise.
We previously reported that 8-year-old children with specific language
impairment (SLI) or central auditory processing disorder (CAPD) had
normal detection thresholds for a 200-ms, 1-kHz tone simultaneously
masked by a 300-ms bandpass noise (0.6-1.4 kHz; N0=40 dB SPL), but
had higher thresholds than 8-year-old controls for a 20-ms, 1-kHz tone
simultaneously, backward, or forward masked by that noise. Here we

ARO Abstracts 31 Volume 25, 2002
frequency of mEPSPs; 2) completely antagonized by cholinergic
antagonists known to block
9/10-nAChRs, and; 3) converted into an
excitatory response following superfusion with selective SK blockers.
During SK blockade, efferent stimulation produces a large depolarizing
postsynaptic potential (PSP) that is also completely blocked by
nAChR antagonists. A portion of the efferent-mediated depolarization
may be postsynaptic (i.e. efferent to afferent) because the PSP is not
completely abolished by glutamate-receptor antagonists that appear to
eliminate quantal transmission from hair cells. Since the remaining
efferent-mediated depolarization is also completely antagonized by
9/10-nAChRs blockers, the same nicotinic receptors may
underlie both
the presynaptic and presumed postsynaptic components. Efferent-
mediated excitation of calyx afferents is characterized by a large
postsynaptic depolarization without an appreciable change in mEPSP
frequency. Unlike efferent responses in bouton afferents, the excitation
of calyx afferents is not very sensitive to
9/10-nAChR antagonists.
(Supported by NIH DC 02058-06 and T-32DC 00058-01).
Position-dependent expression of L and non-L Ca
currents by hair cells of frog semicircular canals
*Ivo Prigioni
, Giancarlo Russo, Andrea Lelli, Department of
Physiological and Pharmacological Sciences, University of Pavia,
Via Forlanini 6, I-27100 Pavia, 27100 Italy
The properties and the distribution of Ca
currents were studied using
the whole-cell variant of the patch-clamp technique in hair cells of frog
crista ampullaris. The currents were recorded in thin slice preparations
and examined in peripheral, intermediate and central cells of the
sensory epithelium. Two classes of cells were found: one exhibiting
partially inactivating Ca
currents and one displaying sustained Ca
currents. Almost all central cells showed inactivating currents, while
about 35% of intermediate and peripheral cells displayed non-
inactivating currents. Ca
current magnitude was in average invariably
larger in intermediate cells (320 pA) than in central (160 pA) and
peripheral (110 pA) cells. In cells showing inactivating currents two
current components could be detected: a sustained L current
sensitive to 5
M nifedipine and a partially inactivating non-L
component insensitive to conotoxin GVIA, conotoxin MVIIC and
agatotoxin IVA. Similarly, cells exhibiting non-inactivating Ca
currents showed a L and a non-L component. In all cells the L
component represented the maximal current (70%). Both L and non-L
component activated close to ñ60 mV, showed rapid time course of
activation (tau-L, 0.60 ms; tau-non-L, 0.45 ms) and r
eached a maximal
value at ñ20mV. The magnitude of L and non-L currents significantly
varied among peripheral cells. Current density was very small in cells
located at the beginning of the peripheral region and increased gradually
becoming maximal at the opposite end. No significant gradient of Ca
current density was detected among intermediate and central cells.
These results demonstrate the presence in frog crista ampullaris of
regional and intraregional variations in the expression of different types
of Ca
channels. It is likely that such differential distribution represents
a mechanism which sustains the variation in the gain and in static and
dynamic properties of vestibular afferent discharge.
Differential Expression of Voltage-Dependent
Currents by Hair Cells from the Frog Utricle and Canal
*Paola Perin
, Sergio Masetto, Paolo Valli, Department of Cell and
Molecular Physiological and Pharmacological Sciences, Section
of General Physiology, Pavia, PV 27100 Italy
Within each vestibular sensory epithelium, currents expressed by hair
cells vary from the center to the periphery. This regionalization has
been well studied in the semicircular canal, but much less in the
otolithic organs. In the pigeon, type II hair cells from corresponding
regions of canal and utricle epithelia appear to express similar currents
(Weng and Correia 1999). However, since other vestibular hair cell
properties differ between amniotes and anamniotes, this similarity may
not be conserved through evolution. To test this hypothesis, we
compared the whole-cell currents expressed in hair cells from the frog
utricle and canal.
Our results suggest that, in the frog utricle, the expression pattern of IA,
ICa, and IK(Ca) are similar as in the canal, with IA being largest in the
periphery and ICa/IK(Ca) in the striola. On the other hand, all other
currents differed in distribution (IK1) or in both distribution and nature
(INa, delayed rectifiers) from those of canal hair cells. Two currents
(INa, IKvs) appeared to be unique to the utricle, whereas the main
delayed rectifier (IKva) was pharmacologically similar the IKv
expressed in the saccule. Differently from the canal delayed rectifiers,
IKva was largest in the extrastriolar cells.
A Voltage-dependent Sodium Channel in Type II
Cells of the Rodent Utricle
*Julian R Wooltorton
, Robert W Schneider, Ruth Anne Eatock,
Department of Otolaryngology, Baylor College of Medicine, One
Baylor Plaza, Houston, TX 77030
Previously it has been shown that a relatively TTX-insensitive sodium
(Na) channel is present in type II cells of the semi-intact mouse utricle
(1) and in both type I and type II hair cells isolated from the rat crista
(2). These currents are almost completely inactivated at the resting
potential of type II cells (~-60 mV). In semi-intact utricular epithelia
excised from neonatal mice (postnatal days, P, 1-4), whole-cell
recordings from type II hair cells revealed a Na current that can be
activated from -64 mV, suggesting a more positive voltage range of
inactivation. The Na current available for activation from -64 mV was
57.7 ± 8.6% of that available from -124 mV (n=10, mean ± S.E.M.).
Activation curves had a half-maximal activation voltage (V
) of -35.7
± 3.8 mV (n=10). This current may correspond to the TTX-sensitive Na
current that has been reported in type II hair cells in the neonatal rat
utricle (3).
One candidate for the
-subunit for TTX-
sensitive, negatively
inactivating Na channels is the cardiac SCN5A subunit. Preliminary
RT-PCR experiments show that SCN5A message is present at P1 and
P21 in rat vestibular organs (anterior and lateral cristae and the utricle).
Further electrophysiological and molecular biological experiments will
be undertaken to investigate more closely the development and
identities of Na channels in rodent vestibular hair cells.
1. R ̧sch, A. & Eatock R.A. (1997)
Sodium Currents in Hair Cells of
the Mouse Utricle
, pp.549-555 in
Diversity in Auditory Mechanics
, eds.
Lewis, E.R. et al., World Scientific Press
2. Bao H., Goldberg J.M. & Eatock R.A. (1999)
ARO Abstr
3. Lennan, G.W.T., Steinacker, A., Lehouelleur, J. & Sans, A. (1999)
Pflugers Arch – Eur J Physiol
, 40-46.
This work was supported by NIH Grants DC02058 & DC02290.
Hair Cell and Afferent Counts in Rodent Otolith
*Sapan S. Desai
, Anna Lysakowski, Anatomy and Cell Biology,
University of Illinois at Chicago, 808 South Wood Street,
Chicago, IL 60612
Though much is known regarding the anatomy of the utricular macula
(Fern·ndez et al.,
60:167, 1990), precise estimates of hair cell and
afferent numbers are lacking. Our project elaborates utricular macular
morphology by counting the numbers of type I and type II HCs in
mouse, rat, and chinchilla using the disector method. Labeled cells
were also counted in samples of mouse and rat maculae stained using
calretinin immunochemistry, which was shown to label calyx afferents
in chinchilla (Desmadryl and Dechesne,
89:105, 1992) and in 5
other species, and type II HCs in mouse and rat (Desai et al.,
Neurosci. Abst.
26:6, 2000).
Utricular maculae were dissected from mouse (N=3), rat (N=3), and
chinchilla (N=3), and stained using calretinin immunochemistry.
Sensory organs were osmicated, dehydrated, embedded in Araldite

ARO Abstracts
Volume 25, 2002
Halsall, Antony, 733
Halsey, Karin Elizabeth, 394,
Hamann, Ingo, 954, 955
Hampton, Lori, 750
Han, Dongyi, 274, 419
Hancock, Kenneth E, 153
Hansen, Marlan R, 283
Hansen, Stefan, 659
Hanson, Joshua Thomas, 544
Hara, Akira, 365
Hara, Hirotaka, 142
Hardelin, Jean-Pierre, 736
Harding, Gary W, 265, 773
Hardisty, Rachel, 107, 751
Harel, Noam, 446
Harkrider, Ashley Whicker,
Harlan, Richard E, 673, 785
Harlan, Richard E, 792
Harmon, Kelley M, 767
Harms, Michael P, 929
Harper, Nicol S, 420
Harrington, Ian A, 456, 796
Harris, Jeffrey P, 350
Harris, Julie A, 576
Harrison, Jeffrey L, 355
Harrison, RV, 446
Hart, Heledd, 931, 932
Hartley, Douglas Edward
Hugh, 747
Hartmann, R, 444, 656
Harwell, Ross M, 748
Hasebe, Seishi, 345, 584
Hashino, Eri, 277
Haslwanter, Thomas, 122,
Hatfield, James S, 308
Hato, Nahito, 207
Hattori, Taku, 348, 870
Hawkins, David, 810
Hawkins, Joseph E, 129
Hawley, Monica L, 930
Hayashizaki, Yoshihide, 86
Hayes, Erin A, 198
Hayes, Jay, 847
Hay-McCutcheon, Marcia
Jean, 178
He, David ZZ, 625, 967
Heaney, Denise LaMarche,
Hebda, Patricia A, 215, 838,
Hébert, Jean M, 724
Hedrick, Mark S, 557
Hefeneider, Steven H, 338
Heffner, Henry E, 456, 796,
Heffner, R S, 797
Heid, S, 444
Heijden, Marcel van der, 329
Heil, Peter, 920
Heinemann, Stephen F, 35
Heinz, Michael G, 331
Heller, Laurie, 772
Henderson Sabes, Jennifer,
Henderson, Donald, 406, 407,
408, 865, 874
Hendricson, Adam W, 363,
Henkel, Craig K, 667
Henry, Belinda A, 458
Henry, J H, 40
Henson, Miriam M, 390, 583
Henson, O’Dell W, 390, 583
Henzl, Michael T, 12
Herdman, Susan J, 487
Hergils, Leif, 249
Herminghaus, S, 444
Herrlin, Petra, 106
Herrmann, Barbara S, 896
Hertzano, R, 567
Herzog, Michael, 18, 19
Higashiyama, Kasumi, 302
Highstein, Stephen M, 125,
Hill, Penny, 73
Himeno, Chiemi, 864
Hind, Joseph E, 549
Hinrichs, Steven H, 641
Hirahara, Tatsuya, 63
Hirano, Shigeru, 881
Hirano, Tomoo, 364, 519
Hirose, Keiko, 400
Hirsch, Barry E, 189
Hirvonen, Timo Petteri, 513,
Ho, Samuel B, 843
Hoefling, Nickoleta L, 258,
349, 871
Hoff, Jessica S, 288
Hoffer, Michael E
486, 517, 887
Hoidis, Silvi, 281
Holley, Matthew C, 289, 290,
Holme, Ralph, 751
Holmes, Steve D, 923
Holt, Avril Genene, 783, 784
Holt, Joseph Christopher,
115, 116, 117, 480
Homanics, Gregg E, 412
Homer, Louis, 953
Honda, Masaaki, 201
Hong, Jenny, 391
Hong, Robert, 461
Hong, Sung Hwa, 635
Hood, Linda J, 375
Hood, Michael, 219
Hoppenbrouwers, Mieke, 891,
Horst, J W, 325
Horwitz, Amy R, 191
Hoshino, Tomoyuki, 872, 875
Hossain, Waheeda A, 285
Houston, Derek M, 5, 173,
Howard III, Matthew A, 549
Howard, MacKenzie Allen,
Hrabe de Angelis, Martin, 103
Hsu, Yun, 410
Hu, Bohua, 406, 407, 408,
Hu, Ning, 657
Hu, Xiaoping, 377
Hu, Zhengqing, 815
Huang, Qing, 469
Huang, Weiguo, 262
Huang, Xinyan, 200
Hubbard, Allyn E, 898
Huber, Alex, 587
Hübner, Mathias M, 800
Hudspeth, A James, 9, 749
Huettenbrink, Karl-Bernd, 245
Hughes, Elizabeth D, 753
Hughes, Larry F, 715
Hughes, Linda M, 772
Hughes, Ruth Marie, 831
Hultcrantz, Malou, 387
Hulvershorn, Leslie A, 801
Hunter, Brian A, 263
Hunter, Lisa L, 837
Hurle, Belen, 752
Hurley, Karen M, 233
Hurley, Laura M, 544
Husain, Kazim, 526
Hussain, Abdulmoshen, 336
Hutchin, Tim P, 96, 97, 372
Hutson, Ken, 670
Huverstuhl, Jochen, 564
Hwang, Chan Ho, 187
Hwang, Soon Jae, 299
Hynes, Michael L, 339
Hyson, Richard L, 701
Idrizbegovic, Esma, 786
Ignatova, Elena G, 352, 353,
Iino, Yukiko, 89
Ikeda, Katsuhisa, 360, 869,
Illg, Angelika, 175
Imagawa, M, 521
Imasato, Akira, 846
Inderkum, Alejandra, 663
Ingala, David, 367
Ingham, Neil, 420
Inglis, J Timothy, 492
Ingo, Todt, 613
Inoue, Makoto, 881
Inoue, Yasuhiro, 402
Intrator, Nathan, 799
Irfan, Nashwa, 430
Irons-Brown, Shunda Renee,
Ishibashi, Toshio, 276, 835,
Ishida, Yuya, 973
Ishige, Ikuo, 89
Ishimaru, Kotaro, 615
Ishimoto, Shin-ishi, 579
Ishiyama, Akira, 378, 479
Ishizu, Koichi, 881
Ison, James R, 713, 714
Issing, Peter, 175
Ito, Juichi, 135, 137, 291, 364,
519, 551, 812, 816, 817, 881
Ito, Ken, 413
Ives, Elizabeth, 101
Iwasa, Kuni H, 629, 719
Iwasaki, Satoshi, 872, 875
Iyer, Nandini, 82
Izumikawa, Masahiko, 864
Jackson, Gale, 219
Jackson, Ronald Lee, 398,
512, 862
Jacobson, Gary P, 964
Jacomme, Anne-Valérie, 28,
Jaeger, Rudi, 122
James, Askew, 369
James, Christopher J, 471
Janssen, Thomas, 764, 774,
Jastreboff, Margaret M, 965,
Jastreboff, Pawel J, 965, 966
Jean, Ronald P, 915
Jenison, Rick L, 549
Jennings, Richard, 882
Jensen-Smith, Heather C,
Jenstad, Lorienne, 208
Jeon, Sang-jun, 511
Jero, Jussi, 252
Jesteadt, Walt, 678, 679, 738
Jewett, Don L, 554
Jeyabalan, Anandhi P, 728
Jia, Shuping, 625
Jiang, Haiyan, 113, 140, 867
Jiang, Hao, 856
Jiang, Hongyan, 133
Jiang, Sichang, 274, 419
Jiang, Zhi-Gen, 304, 873
Jianhe, Sun, 240
Jin, Xiaojie, 414
Jinn, Taehoon, 836
Jiradejvong, Patpong, 514
John, Earnest O, 141, 836
Johnen, Anja, 50
Johnson, Ann-Christin, 106
Johnson, Claire M, 733
Johnson, Eric M, 916
Johnson, Kenneth R, 105,
110, 482
Johnson, Krista L, 561
Johnson, Linda, 841
Jones, Christine E, 203
Jones, Gavin E, 398, 512
Jones, Jennifer, 292
Jones, Sherri M, 482
Jones, Timothy A, 242, 482
Jono, Hirofumi, 844, 846
Joris, Philip X, 329
Judice, Tiffany N, 609
Juhn, Steven K, 263
Jung, Hak Hyun, 299, 840
Jung, Jae Yeon, 831, 834
Jung, Seul Ki, 840
Jung, Timothy TTK, 141, 836
Junker, Ruediger, 613
Kacelnik, Oliver, 801
Kachar, Bechara, 13, 87, 600,
624, 811, 972
Kaga, Kimitaka, 210, 276,
835, 845, 858, 878
Kageyama, Ryoichiro, 817
Kaiser, Adam R, 470
Kaiser, Alexander, 672
Kaiser, Christina Lynn, 821
Kakehata, Seiji,
Kakigi, Akinobu, 302
Kakrlapudi, Venkatesh, 510
Kalinec, Federico, 139, 855
Kalinec, Giloa M, 139, 855
Kallman, Jeremy C, 95
Kaltenbach, James, 788, 791
Kammen-Jolly, Keren, 294,
362, 385, 572, 573
Kanaan, Moien, 98
Kandler, Karl, 698, 699
Kang, Eunjoo, 187
Kang, Sung-Ho, 848
Kanicki, Ariane C, 256, 382
Kanwal, Jagmeet S, 152, 167,
Kanzaki, Jin, 402
Kanzaki, Sho, 416, 579, 813
Kapadia, Sarosh, 324
Kappler, James A, 749
Kaprielian, Zaven, 730
Karavitaki, Kiriaki D, 632
Karino, Shotaro, 210
Karpenko, Andrew N, 237
Kashino, Makio, 47, 63
Kassemi, Mohammad, 128
Katbamna, Bharti, 866
Kathju, Sandeep, 581
Katz, Eleonora, 611
Kaufman, Kenton R, 880
Kawa, Jun, 86
Kawamoto, Kohei, 394, 416,
579, 630, 813, 818
Kawano, Hirokazu, 843
Kawasaki, Hiroto, 549
Kawase, Tetsuaki, 829
Kaylie, David M, 644
Ke, Xiao M, 366
Keane, William M, 580
Keats, Bronya J, 369, 375
Keddache, Mehdi, 367
Kee, Renee, 536
Keithley, Elizabeth, 350, 391
Kelley, Matthew W, 292, 732,
Kelley, MF, 568
Kelley, Philip M,
Kelly , Kristin A, 448
Kelly, Jack B, 661, 664
Kelly, John K, 327
Kelly, Thomas C, 526
Kelly, William J, 373
Kempton, Beth, 338
Kenna, Margaret Alene, 368
Kentala, Erna L, 488, 886
Kerschner, Joseph Edward,
Kessler, Dorcas, 184
Kevanishvili, Zuriko,
Khan, Khalid M, 308
Khanna, Shyam M, 592
Kidd Jr, Gerald, 681, 682
Kiefte, Michael, 332
Kiernan, B W, 751
Kikuchi, Toshihiko, 615
Kileny, Paul R, 176, 182
Kilgard, Michael P, 439, 440,
Killick, Richard, 12
Kim, Chong-Sun, 187, 214
Kim, Dongwok, 331
Kim, Duck O, 227, 761
Kim, Hyo Joon, 610
Kim, Myung Sun, 635
Kim, Paul, 141, 836
Kim, Seo Jin, 840
Kim, Suh Jin, 299
Kim, Taei-Gyu, 93
Kim, Tesu, 135, 137, 812,
816, 817
Kim, Theresa B, 570
Kim, Won Tae, 610
Kim, Youngki, 842, 843
Kimberling, William J, 369,
370, 373, 374
Kim-Lee, Yukyoung, 472
Kimura, Yurika, 89
King, Andrew J, 45, 66, 163,
671, 801
King, Curtis, 125
King, Cynthia D, 199
King, Darren P, 386, 570
King, Isabella, 805
King, Mary-Claire, 98, 101
King, Wayne M, 779
Kirk, Des, 506
Kirk, Desmond L, 321, 323
Kirk, Edward Christopher, 313
Kirk, Karen I, 7, 173, 472
Kirner, Alexandra, 640, 814
Kirschhofer, Karin, 369
Kirshner, Howard S, 559
Kirstein, Mark Noel, 219
Kitamura, Ken, 89, 499
Kittel, Malte, 804, 954, 955
Klass, Patricia, 75
Klinke , Rainer, 445
Klinke, R, 444, 656
Kloecker, Nikolaj, 967
Kluender, Keith R, 332
Klug, Achim, 51, 544
Klump, Georg M, 804, 807,
954, 955
Knight, Richard D, 212
Knipper, Marlies, 91, 272,
627, 633, 937
Koay, G, 797
Kobayashi, Daisuke, 89
Kobayashi, Toshimitsu, 360,
829, 869
Koch, Dawn Burton, 183, 645
Koch, Ursula F, 660
Koehnke, Janet D, 949
Koeppl, Christine, 502, 507,
Koepschall, Iris, 272
Kofuji, Paulo, 756
Kohrman, David C, 108, 110,
Koike, Takuji, 829
Kojima, Ken, 291
Kolb, Hans-Albert, 613
Kollmar, Richard, 749
Komeda, Mototane, 864
Kommareddi, Pavan K, 349
Kong, Wei-Jia, 385
Konishi, Masakazu, 424
Koo, Ja-Won, 187, 412
Kopco, Norbert, 53, 61
Kopke, Richard D, 398, 486,
512, 861, 862
Köppl, Christine, 427
Kössl, Manfred, 160, 311, 770

ARO Abstracts
Volume 25, 2002
Kotak, Vibhakar C, 697
Kozlova, Elena N, 815
Kozma, Kelley E, 258, 871
Kral, A, 444
Kral, Andrej, 445
Kraus, Nina, 41, 198, 199,
539, 558, 561
Kreft, Heather A, 465
Kretzmer, Erika, 29
Kreuzer, Judith, 695
Krishnan, Ananthanarayan,
Kristiansen, Arther, 100
Kristiansen, Kris, 496
Kroll, Kai, 590, 591
Kros, Cornelis J, 238, 602
Kruger, Tracey, 183, 184
Kruse, Eberhard, 437
Krynetskiy, Evgueni, 219
Kubke, M Fabiana, 425, 426
Kubli, Lina R, 743
Kubo, Takeshi, 438
Kuhn, Christian, 934
Kujawa, Sharon G, 104, 896
Kulesza Jr, Randy J, 422
Kulikovskaya, Nina, 126
Kulkarni , Ashok, 639
Kullmann, Paul HM, 699
Kurima, Kiyoto, 750
Kuriyama, Hiromichi, 864
Kurtzberg, Diane, 695
Kusakari, Jun, 365
Kuwabara, Nobuyuki, 666
Kuwada, Shigeyuki, 49, 206
Kvasnak, Eugen, 146
Kwiek, Stanislaw, 778
Lallemend, François, 286
Lalwani, Anil K, 252
Lampacher, Peter, 39
Lan, Zhang, 404
Lanahan, Anthony, 87
Lanfermann, H, 444
Lanford, Pamela J, 292
Lang, Hainan, 268, 530, 532
Langemann, U, 807
Langner, Gerald, 164, 665
Lansford, Christopher D, 258
Lapsley M
iller, Judi A,
Larson, Jonathan, 27
Larson, L J, 554
Larson, Sandra, 859
Lasker, David, 514
Lasker, David M, 515
Lau, Christina, 391
Lauer, Amanda M, 806
Laurell, Goran, 20, 395, 860
Laurell, Goran Frans
Emanuel, 854
Lawoko-Kerali, Grace, 289
Le Prell, Colleen Garbe, 630
Leake, Patricia A, 3, 646, 647,
Leal, Suzanne M, 369
Lear, Patricia Marie, 257, 264
Lechene, Claude P, 617
Lee, Chung-Yi, 243
Lee, Daniel J, 794
Lee, Dong Soo, 187
Lee, Haa-Yung, 830, 848
Lee, Heungman, 299
Lee, Hyo Jin, 706
Lee, Hyosang, 607
Lee, Jae Sung, 187
Lee, James, 188
Lee, Jeong Woong, 635
Lee, Jun-Ho, 15, 16, 18
Lee, Kenneth H, 415
Lee, Ming K, 98, 101
Lee, Sea Hyung, 263
Lee, Yun-Shain, 297
Lee, Yun-Woo, 263
Leek, Marjorie R, 743, 806
Leem, Chae Hun, 610
Lefebvre, Philippe Pierre, 286
Lehar, Mohamed, 392
Leibold, Lori, 680
Leitner, Alexander, 689
Lelli, Andrea,
Lentz, Jennifer J, 743, 806
Lenzi, David, 619
Leonova, Elena V, 386, 388,
Lesniak, Wojciech Gracjan,
132, 859
Lesperance, Marci M, 570
Leuwer, Rudolf, 112
Levine, Robert Aaron, 340,
Levine, Samuel Charles, 377
Lewis, Edwin R, 921
Li, F, 810
Li, Geming, 527
Li, Ha Sheng, 361, 849
Li, Hongzhe, 147
Li, Jian-Dong, 830, 844, 846
Li, Lijun, 279
Li, Mingyuan, 90
Li, Qingxia, 418
Li, Shengguo, 562
Li, Yan, 295
Liang, Cindy J, 513
Liang, Fenghe, 389, 616
Liang, Jain-Ning, 639, 851
Liang, Li, 453
Liao, J, 278
Liberman, M Charles, 104,
224, 307, 400, 910
Liebl, Daniel J, 253
Lifton, Richard, 948
Lilaonitkul, Watjana, 314
Lim, David J, 139, 768, 830,
Lim, Dukhwan, 214
Limberger, Annette, 272
Limón Ruíz, Agenor, 114
Lin, Aaron, 831, 834
Lin, Feng, 565
Lin, Jizhen, 293, 842, 843
Lin, Xi, 418, 925
Lindblad, Ann-Cathrine, 254
Linder, Birgitta, 11, 417
Lindgren, Bruce R, 837
Lindholm, Dan, 417
Lindsay, Fred, 582
Linthicum, Frederick, 830
Lioudyno, Maria, 480
Lisowska, Grazyna, 315, 778
Lister, Jennifer Jones, 950
Litovsky, Ruth Y, 467
Liu, Feng, 297
Liu, George, 843
Liu, J, 861, 862
Liu, Jianzhong, 398, 512
Liu, Wei, 278, 279, 527
Liu, Xue Zhong, 100, 366,
Liu, Yu H, 366
Lobarinas, Edward, 685
Lockridge, Oksana, 641
Lockwood, Alan H, 550
Loeb, Gerald E, 653, 654
Loewenheim, Hubert, 640,
Lofgren, Melissa M, 700
Lomax, Catherine A, 386
Lomax, Margaret I, 256, 258,
382, 386, 388, 570, 636, 783
Long, Christopher J, 462
Long, Glenis R, 335
Long, Kevin B, 623, 968
Lonsbury-Martin, Brenda L,
253, 265, 643
López, Edith, 702
Lopez, Ivan A, 378, 479
Lopez, Lanier, 13
Loquet, Gérard, 38
Loughlin, Patrick J, 890
Lovett, M, 810
Lu, Jianzhong, 22
Lu, Thomas, 453
Lucas, Jeffrey R, 335
Lucke, Claudia, 435
Luduena, Richard F, 941
Ludwig, Jost, 967
Ludwig, Sara M, 785
Luebke, Anne E, 309
Lugert, Elizabeth C, 374
Lurie, Diana I, 705
Lusis, A Jake, 94
Lutfi, Robert A, 683
Luxon, Linda M, 956, 957
Ly, Dune, 87
Lynch, Eric, 101
Lynch-Erhardt, Martha A, 710
Lyon, Michael J, 202
Lysakowski, Anna, 121, 234
Ma, Chun-Lei, 661
Ma, Ellen, 777
Ma, Wei-Li Diana, 596
MacDermot, Kay D, 639
MacDonald, Richard B, 619
Macfarlane, David S, 471
Mack, Andreas, 627
MacLaren, Linda, 101
Maconochie, Mark K, 726
Madison, Laird, 623, 968
Madnani, D
Mahendrasingam, Shanthini,
Maier, Hannes, 346
Maison, Stéphane F, 307
Major, Ronald, 398
Major, Ronald L, 512
Maki, Katsuhiro, 47
Makishima, Tomoko, 750
Malec, James F, 880
Maleki, Lili,
Malgrange, Brigitte, 286
Malmgren, Leslie T, 203
Malmierca, Manuel S, 667
Mangiardi, Dominic, 130, 138,
Manis, Paul B, 34, 787
Mankarious, Leila A, 216
Manley, Geoffrey A, 321, 502,
507, 593, 628
Mansour, Suzanne L, 568,
Marcotti, Walter, 602
Marcus, Daniel C, 15, 16, 18,
301, 571, 736, 756, 757
Margolis, Robert, 837
Marquardt, Torsten, 55, 687
Marsch, Rudolph, 160
Marsh, Robert A, 37
Marshall, Lynne, 772
Martin, Brett A, 695
Martin, Eduardo, 885, 958
Martin, Gail R, 724
Martin, Glen K, 253, 265, 643
Martin, Kareen, 723
Martin, Lois FA, 471
Martin, Paul, 141, 836
Martin, Russell L, 54
Martin, William H, 914
Maruyama, Jun, 658
Marvit, Peter, 675
Marz, Alexis, 339
Masaki, Kinuko, 916
Masetto, Sergio, 119
Mason, Christine R, 681, 682
Masuda, Masako, 618
Mathers, Peter H, 704
Matsubara, Atsushi, 365
Matsuda, Ke
623, 968
Matsui, Jonathan I, 261
Matsunobu, Takeshi, 402
Matthews, Scott K, 908
Mattila, Mary Kay, 790
Mattox, Douglas, 351
May, Bradford J, 190, 795,
May, Kara E, 130, 820
Mburu, Philomena, 751
McAlpine, David, 55, 154,
155, 420
McAnally, Ken I, 54
McCaslin, Devin L, 964
McConnell, Susan K, 724
McCoy, Sharon L, 338
McFadden, Sandra, 113, 140,
259, 578, 867
McFarland, Dennis J, 555
McGee, JoAnn D, 637, 641
McGuirt, Wyman T, 498
McIntosh, J Michael, 480
McInvale, Andrew
Christopher, 673
McKay, Colette M, 462
McKenna , Michael J, 496
McNaboe, Edward J, 394
Meddis, Raymond, 923
Medley, Tina, 895
Medvedev, Andrei V, 152,
Meenderink, Sebastiaan, 771
Meetze, Keith A, 532
Melcher, Jennifer R, 929, 930
Mendelson, Julie R, 706
Meng, H, 521
Menon, PSN, 750
Merchán, Miguel A, 667
Merchant, Saumil N, 500
Merfeld, Daniel M, 516
Merkle, Hellmut, 377
Merritt, Raymond C, 624
Merritt, Sarah, 324
Messana, Elizabeth P, 261
Meyer, Amy, 888
Meyer, Michaela, 42
Meyer, Tanya Kim, 850
Meyer, Ted A, 473
Meyer-Bisch, Christian, 273
Meyers, Erik N, 724
Meyers, Jason R, 619
Mhaskar, Yashanad, 945
Mhatre, Anand Nilkanth, 252
Michaels, Leslie, 639, 851
Middlebrooks, John C, 541
Miles, Matthew, 484
Milhaud, Pierre G, 18
Miller, Antonio J,
Miller, Charles A,
649, 652,
Miller, Josef M, 255, 405, 417,
658, 815, 854, 926
Lee Mathew, 686
Miller, Nat
haniel, 371
Miller, R
oger L, 179, 654,
655, 763
Miller, Teya A,
Millman, R
ebecca, 79
Mills, David M,
Mills, Gilda I, 654
Mineta, Hiroyuki, 872
Mino, Hiroyuki, 649
Minoda, Ryosei, 618
Minor, Lloyd B, 513, 514, 515,
Mire, Patricia L, 601
Mishler, Pamela Jean, 65
Mitchell, C R, 40
Mitchell, Kelly W, 34
Mitchem, Kristina, 108, 110
Miura, Makoto, 189, 345
Miyabe, Yuka, 615
Miyamoto, Richard T, 173,
Mizuta, Kunihiro, 872
Mlynski, Gunter, 218
Mlynski, Robert Arndt, 218,
Mo, Jianhong, 750
Moeller, Sebastian, 548
Moessner, Anne M, 880
Moll, Ingrid, 112
Moller, Claes G, 373
Mom, Thierry, 758
Moncrieff, Deborah W, 560
Monobe, Hiroko, 835, 845
Montcouquiol, Mireile E, 732
Moody, David B, 630
Moon, Sung-Kyun, 830, 848
Moonen, Gustave, 286
Moore, Brian CJ, 677, 745
Moore, Charlotte M, 646, 647
Moore, David Robert, 73, 740,
747, 801
Moore, Jordan, 56
Moore, Robert J, 486
Morawski, Krzysztof, 305,
306, 315, 778
Morell, Robert J, 87
Morest, D Kent, 27, 285
Morita, Takeshi, 551
Morr, Mara, 695
Morrison, Adrian R, 10
Morrow, Bernice, 278
Moser, Tobias, 608, 621
Moss, Cynthia F, 57, 58, 59,
Mostafapour, Sam P, 700
Moucha, Raluca, 439, 441
Mount, RJ, 446
Mountain, David C, 138, 596,
632, 820, 898
Mroz, Edmund A, 617
Mrsic-Flogel, Tom D, 66
Mueller, Marcus, 640, 814
Mueller, Robert Frederick, 96,
97, 372
Muenkner, Stefan, 238
Mugnaini, Enrico, 754
Mullen, Lina M, 282, 295, 564
Muller, Barbara S, 428
Müller, Jörg, 774
Mundinger, Paul C, 947
Munson Jr, Robert S, 841
Murai, Norihiko, 135, 137,
364, 519, 812, 816, 817
Murano, Emi, 201
Murnane, Owen D, 327, 895
Murphy, Emily, 485
Muse, Pablo, 342
Nagamine, Takashi, 551
Nagura, Mitsuyoshi, 848, 872,
Nair, Thankam S, 258, 339,
349, 871
Naito, Yasushi, 364, 519, 551,
Nakagawa, Takayuki, 135,
137, 812, 816, 817
Nakajima, Haruhiko, 904
Nakamori, Akiko, 365
Nakashima, Tsutomu, 303,
348, 870
Namba , Atsushi, 370
Namyslowski, Grzegorz, 315,
Nance, Melonie Adia, 831,
Nance, Walter E, 100, 366,
Narain, Charvy, 194
Narins, Peter M, 334
Nash, Donald J, 509
Nasse, Jason, 601
Nassiri, Reza, 686
Nataraj, Kiran, 144
Navarrete, Enrique, 623, 968
Navarro Coy, Nuria, 97
Naz, Sadaf, 750

Association for Research in Otolaryngology
Executive Offices
19 Mantua Road
Mt. Royal, NJ 08061
Phone (856) 423-0041(856) 423-0041 FAX (856) 423-3420
E-mail: Website:
by JF Battey
For information on alternatives to aspirins or antibiotics, check out