The dorsal cochlear nucleus (DCN) is a relatively complex neural region thought to provide rapid and early processing of complex acoustic stimuli, and to associate auditory and non-auditory events. The overall goals of this grant are to investigate cellular mechanisms of information processing in the molecular layer of this nucleus. This circuitry consists of an obligatory set of interneurons, the granule cells, which receive input from diverse mossy fiber afferents and in turn form excitatory parallel fibers that innervate two major targets: a set of inhibitory neurons, the cartwheel cells, and the principal projection neurons of the nucleus, the pyramidal cells. The pyramidal cells are the final common pathway through which this intricate neural circuit processes acoustic information, and provide a direct and significant input to the principal auditory midbrain nucleus, the inferior colliculus. The current proposal focuses on the intrinsic integrative mechanisms of pyramidal cells.
The first aim i s to investigate the hypotheses that the voltage-dependence of pyramidal discharge patterns depends on the voltage-dependence of a rapidly inactivating potassium conductance present in these cells. The modifiability of this conductance and its effects on discharge patterns, as well as sensitivity to peptide toxins, will also be studied.
The second aim i s to investigate the hypothesis that subthreshold oscillations in the membrane during slow depolarization play a role in regulating the first spike latency and first interspike interval, and to determine the ionic basis of the oscillations.
The third aim i s to evaluate the hypothesis that conductances operating in different voltage regimes differentially participate in the dynamic integration of synaptic inputs, using dynamic current clamp.
The fourth aim i s to continue development of single-cell models of pyramidal cells based on experimental results and to use those models to evaluate experimental results and develop new hypotheses. These experiments utilize patch-clamp recordings from cells in brain slices, including current and voltage-clamp studies on outside-out patches, high-speed calcium imaging, and pharmacological manipulations. These experiments will help us to understand key cellular mechanisms involved in neural integration of information by an important class of cells in the cochlear nucleus. The results will have an impact on our understanding of information processing in the DCN and its dynamic characteristics, and may suggest new functions for this primary auditory center. These studies may also lead to new knowledge about the general rules of information processing by neurons throughout the central nervous system.
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