INFORMATION PROCESSING AT AUDITORY NERVE SYNAPSES
XU-FRIEDMAN, MATTHEW A. Principal Investigator
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Sounds are encoded by the cochlea in the timing of spikes in the auditory nerve. Auditory nerve fibersconverge onto bushy cells in the cochlear nucleus, through synapses called 'endbulbs of Held'. Thisconvergence leads to changes in the timing information passed on by bushy cells to higher auditory centers,which may affect sound localization and processing. Experiments have indicated that the timing of bushycell spiking is greatly affected by the size of the endbulb synaptic current, which is subject to two majorinfluences in vivo. First, endbulb synapses show considerable depression when activated at normal rates.Second, they are subject to a number of neuromodulatory systems. Both these influences can affect theinformation carried by bushy cells, but neither is well understood. The specific aims of this project are todetermine (1) the dynamics and mechanisms of use-dependent changes in the endbulb synaptic current, (2)how the different components of the synaptic current control bushy cell timing, and (3) how neuromodulationchanges these relationships. This work will be carried out using patch-clamp recordings of bushy cells inbrain slices taken from mice and gerbils. The mechanisms of depression will be considered first, by testingthe contributions of presynaptic vesicle depletion and postsynaptic receptor desensitization and saturation.In addition, an unusual form of depression at the endbulb will be examined, which has been proposed toinvolve reduced presynaptic calcium influx, but has never been directly tested. It will also be determinedhow depression could be mitigated by both facilitation and the activation of NMDA receptors. In addition,current- and dynamic-clamp studies will test whether delayed release during high levels of activity disruptsthe precisely timed responses of bushy cells. Taken together these studies will provide importantinformation about the mechanisms by which timing information is transformed by convergence of auditorynerve synapses during realistic activity.This work will examine the mechanisms used by cells in the cochlear nucleus to process sound information.It will also provide important insights into the functional role that different receptor types andneuromodulatory systems play in neuronal computation. This work may lead to improvements both inexisting cochlear implants and in implants that stimulate the cochlear nucleus directly.