The first stage of information processing in the central auditory system is mediated by the neural circuits and membrane properties of cells in the cochlear nucleus. One subdivision of the cochlear nucleus, the dorsal cochlear nucleus (DCN), has a particularly complex internal architecture, and the responses of cells in the DCN to acoustic stimuli are substantially modified from their eights nerve inputs. In most superficial layer of this nucleus, a system of fine unmyelinated parallel fibers (axons of granule cells.) make numerous synapses upon the principal projection neurons of the DCN (pyramidal cells) and small interneurons (cartwheel and stellate cells). The parallel fibers provide the substrate for a unique and extensive set of interactions occurring orthogonal to the tonotopic axis of the DCN. It is likely that the parallel fiber system plays an important role in shaping the complex receptive fields and temporal response patterns of the DCN pyramidal cells. In order to understand how the granule cells and their associated local circuitry can influence pyramidal cells, we are studying responses to electrical stimulation of the axons of the granule cells, the parallel fibers. The experiments in this proposal investigate four specific aspects of parallel fiber influences on DCN neurons both in an in vitro brain slice preparation, and in vivo. First, extra- and intracellular recordings will be made from single DCN neurons to study synaptic responses to parallel fiber stimulation. Subsequent to intracellular recordings, neurons will be stained for morphological identification. Responses will be correlated with cell type and laminar position. Second, current source=density analysis will be used to determine the spatial and temporal distribution of current sinks and sources produced by electrical stimulation of the parallel fibers at the pial surface of the nucleus. This analysis will reveal the laminar distribution of synaptic connections between the parallel fibers and DCN neurons. Third, pre- and post-synaptic mechanisms influencing synaptic potentiation at the parallel fiber synapse will be explored. The time course of potentiation will be determined. Fourth, the pharmacology of excitatory synaptic transmission from parallel fibers to their postsynaptic targets, and also of possible inhibitory amino-acid local circuits that can be activated by parallel fibers in the DCN molecular layer, will be investigated. The results of these studies will provide important information on the role of the parallel fiber system in the DCN, and will help 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, as well as investigations of the synaptic plasticity and membrane biophysics of DCN neurons.
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