Mapping the Connectivity of Cochlear Nucleus Bushy Cells

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): There is a growing appreciation that developing improved cochlear implants and treatments for tinnitus depends on understanding how information is processed in the central auditory nuclei. The cochlear nucleus receives direct input from the auditory nerve, and is one of the most thoroughly studied nuclei in the brain. Its cell types are distinct and its connections are highly stereotyped. Surprisingly, knowledge about synaptic connectivity within the nucleus is rather limited, which has impeded progress in understanding its role in information processing. This proposal examines the function and organization of local circuitry in the anteroventral cochlear nucleus (AVCN). Recent literature describes many different and often conflicting theories about circuit function in the AVCN. In the first aim of this proposal, the connectivity and synaptic kinetics of cells in the AVCN will be examined using focal glutamate uncaging in cochlear nucleus slices. These experiments will reveal basic details about the structure of the AVCN circuit that have previously eluded examination. Of particular interest are the connections from dorsal cochlear nucleus tuberculoventral neurons and local D-stellate neurons. To investigate the functional significance of AVCN circuitry, a computational model of the network will be built based on accurate representations of synaptic kinetics, neuronal membrane properties, and connectivity patterns. This model will be used to compare the abilities of tuberculoventral and D-stellate neurons in basic psychophysical paradigms. Currently no cochlear nucleus network models use biologically determined synaptic kinetics and connectivity. We aim to provide a model that is as physiologically accurate as possible, allowing greater insight into tinnitus, cochlear implantation, and auditory processing. PUBLIC HEALTH RELEVANCE: Our understanding of the auditory system has driven the development of hearing aids and cochlear implants. Progress is currently limited by our poor understanding of the processing that takes place in the auditory brainstem. This research will determine the structure of auditory brainstem circuits and use this information to investigate auditory information processing.