The transmission of acoustic information through synapses in the cochlear nuclei is robust yet also adaptable. The robustness of synaptic transmission allows ongoing acoustic information to be conveyed without its being obscured by the synaptic traffic that encoded previous sounds. However, transmission of acoustic information is also known to adjust between quiet and noisy environments, to the position of the head and ears, and to hearing loss. In slices from mice we propose to examine to what extent, over what time course, and under what conditions synapses in the first integrative stage of the auditory pathway are stable and how they are modified by synaptic activation and neuromodulation. Two contrasting systems of inputs, myelinated auditory nerve fibers and unmyelinated parallel fibers, are major sources of excitation in the cochlear nuclei. For these two systems we propose to examine plasticity that occurs over milliseconds to minutes (short-term plasticity), over minutes to hours (long-term plasticity), and over hours to weeks (homeostatic plasticity). At the cellular level we seek to understand the differences in the way the strength of synapses from auditory nerve fibers and parallel fibers is regulated. Studies of calyceal synapses have documented synaptic depression but it is unclear whether the properties of synapses are similar at all targets and to what extent synaptic depression is evident at mature synapses. Are these synapses affected by neuromodulators? Synapses from parallel fibers show bidirectional short-term and long-term plasticity. Is this plasticity limited to active synapses? What are the cellular mechanisms that underly this plasticity? How are synapses from the auditory nerve affected in the long term by deafness? Understanding of how the strength of synapses in the cochlear nuclei is affected by activity is central to understanding normal hearing. It will also bring insight into what changes are produced by deafness and what changes might be associated with maintaining or regaining function through hearing aids and cochlear implants in human patients.
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