The goal is to understand the cellular basis for central processing in specific binaural and monaural circuits of cell types, extending from the cochlear nucleus to the inferior colliculus. either directly or via the nuclei of the superior olive and lateral lemniscus. An interdisciplinary approach will characterize the structural, electrophysiological, and neurochemical properties of these circuits, especially the inhibitory components. The synaptic connections of the cell types will be studied anatomically, while their response properties to acoustic stimulation will be defined physiologically and the related groups of neurons labeled with micromarkers through the recording electrodes. Cytochemical labeling will localize the suspected transmitters in the afferent inputs to these cell types. The contributions of these inputs to the generation of the neuronal responses will be studied by stimulating or blocking them neurochemically in combined anatomical and physiological experiments. The analysis will help to form useful models of the synaptic mechanisms underlying the response properties of each type of neuron in the circuit. This is necessary to explain the cellular mechanisms governing the operation of these circuits in normal perception and their alterations in response to trauma. The reaction of the mature cochlear nucleus to acoustic trauma, as evinced in sensorineural hearing loss due to noise damage of the cochlea, will be assessed in terms of the new growth of axons and the neurochemistry of the transmitters, which may involve inhibitory synapses. Finally the binaural responses of neurons in the inferior colliculus will be analyzed physiologically with acoustic stimuli that are known to elicit the precedence effect. The hypothesis is that the neural events underlying the binaural perceptual effect depend on inhibitory mechanisms in hearing.
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