The long term goals of the applicant are to understand the neurobiologic 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 cochlear nucleus. The studies in this proposal will be carried out in an interdisciplinary environment provided by Neuroscience, Biomedical Engineering and Otolaryngology-Head and Neck Surgery departments and in collaboration with an active group of auditory researchers. This experience will enhance the research abilities of the investigator by permitting more time for the investigator to explore contemporary neurobiological issues related to the cellular basis of information processing by neurons. This experience will also extend the research capabilities of the investigator by permitting the full exploration of new research areas and techniques in which promising preliminary results have already been obtained. In addition, interactions with faculty involved in quantitative biology and mathematical modeling will provide important insights into the experimental issues that must be addressed in creating accurate biologically-based models. Three specific hypotheses about the mechanisms of information processing by neurons in the mammalian cochlear nucleus will be investigated using intracellular, field potential and optical recordings of calcium activity from an in vitro brain slice preparation, and with whole cell tight seal voltage clamp recordings from neurons acutely isolated from the slices. The first experiments will investigate the hypothesis that the activation of a specific subset of excitatory amino acid receptors, the N-methyl-D-aspartate (NMDA) receptors, in the dorsal cochlear nucleus molecular layer may result in the long term modification of synaptic or membrane conductances in postsynaptic cells. The second set of experiments will examine the hypothesis that a non-inactivating sodium conductance and a rapidly inactivating potassium conductance contribute to the complex discharge patterns of dorsal cochlear nucleus projection neurons. The third set of experiments will characterize biophysical properties of a specific outward conductance in bushy cells of the ventral cochlear nucleus. This conductance is likely to be present in other cells of the brainstem auditory system and to play an important role in the preservation of phase information for low frequency sound localization.
