Hair cells in the cochlea connect to auditory afferent fibers via ribbon synapses, which convert presynaptic gracied potentials (analog signal) Into postsynaptic all-or-none spikes (digital signal). The long-term objective of this study is to investigate mechanisms of synaptic transmission and strategies for auditory coding at these synapses. Previously, by determining the quantal size of the hair cell ribbon synapse in bullfrog j amphibian papilla, we demonstrated unequivocally that hair cells can release more than one synaptic vesicle at a time (multivesicular release, MRV) from a single release site (i.e., ribbon). To study cellular mechanisms that control MRV, we will measure the calcium-dependence of MVR and determine its calcium threshold. To demonstrate the functional advantages of MRV, we will first stimulate hair cells with sinusoidal presynaptic depolarizations that mimic hair cell voltage responses in vivo, and quantify MVRs in the evoked EPSCs. Then we simulate two sets of EPSCs in which we either substitute MVRs with evenly distributed single vesicle releases within a time window (e.g., 0.1 ms), or fix the quantal content of MVRs (removing the variation in their quantal contents). We will feed both the original and simulated EPSCs to afferent fibers under current-clamp, and find out to what extent the phase-locking of spikes gets deteriorated. To investigate how synaptic vesicles are recycled, we will use a two-photon microscope to visualize FM1-43 dye loading to monitor vesicle recycling, and we will also make cell-attached capacitance measurement on hair cells to study vesicle recycling by monitoring capacitance changes with a submillisecond time resolution.

Public Health Relevance

In the United States, many thousands of hearing-impaired patients rely on cochlear implants to restore part of their hearing by directly stimulating auditory nerve fibers with electrodes. The studies proposed here will expand our knowledge on how auditory signals are passed onto auditory nerve fibers, and it could provide guidance for significant improvement of cochlea implants.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Transition Award (R00)
Project #
5R00DC010198-04
Application #
8409791
Study Section
Special Emphasis Panel (NSS)
Program Officer
Cyr, Janet
Project Start
2009-07-02
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$236,550
Indirect Cost
$49,000
Name
University of Massachusetts Amherst
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
01003