Our long term goals are to understand the principles which underlie the information processing capabilities of neurons in the central nervous system. The goal of this proposal is to examine mechanisms of information processing in one region of the auditory brainstem, the dorsal cochlear nucleus (DCN). In the most superficial layer of this nucleus, a system of fine, unmyelinated parallel fibers (axons of granule cells) make numerous synapses on the principal projection neurons of the nucleus (pyramidal cells) and on small interneurons (cartwheel and stellate cells). The parallel fibers provide the substrate for unique and extensive interactions occurring orthogonal to the tonotopic axis of the DCN. Four specific hypotheses about the mechanisms of information processing by neurons in the mammalian DCN will be investigated. First, we will investigate the hypothesis that the activation of a specific subset of excitatory amino acid receptors, the N-methyl-D-aspartate (NMDA) receptors, can contribute to nonlinear facilitation of parallel fiber and auditory nerve inputs to pyramidal cells. Second, we will investigate the hypotheses that postsynaptic calcium entry associated with parallel fiber synaptic activity, either through NMDA receptors or voltage-sensitive calcium channels, can result in the long-term modification of synaptic or voltage-dependent conductances in postsynaptic cells. Third, we will test the hypothesis that the voltage- dependent discharge patterns of dorsal cochlear nucleus pyramidal cells are in part produced by a transient potassium conductance. Fourth, we will test the hypothesis that cartwheel cells are inhibitory to pyramidal cells. The experiments to test these hypotheses use intracellular, whole-cell tight-seal, field potential recordings, and optical recordings of calcium activity from an in vitro brain slice preparation, and whole-cell tight-seal voltage-clamp recordings from acutely isolated neurons. The results of these studies will provide important information about the function of the parallel fiber system in the cochlear nucleus, and will help to generate new theories about the role that this system plays in processing incoming acoustic information. These experiments will also set the stage for subsequent investigations of changes in central physiology that may occur as a function of peripheral acoustic trauma and aging.
Showing the most recent 10 out of 22 publications
