In the auditory system of mammals, all information pertaining to sound enters the brain by way of the auditory nerve and terminates in the cochlear nucleus. This nucleus serves as the gateway to the central auditory system by receiving and processing incoming activity and sending output signals through multiple parallel pathways to higher centers. Our long-term research objectives are to determine the neural circuitry established by auditory nerve fibers in the cochlear nucleus, to investigate mechanisms underlying the early stages of acoustic information processing, and to identify the role of hearing on the development of these structures. Intracellular recording and staining methods will be used to label the myelinated auditory nerve fibers in cats. The marking of single fibers with horseradish peroxidase (HRP) after first characterizing their physiological response properties will permit us to make direct comparisons between a fiber's response features, its synaptic morphology, and its connections with projection neurons. By combining single fiber staining with other pathway tracing techniques and immunocytochemical methods, we can determine the organization of auditory nerve input at the single neuron level using light and electron microscopy. The unmyelinated fibers will be labeled by extracellular injections of HRP into the cochlea of rodents to identify their connections to local circuit neurons. Synaptic development in the cochlear nucleus will be studied in a series of age-graded normal and deaf animals. The proposed research will generate new information concerning the anatomic foundations of stimulus coding and neural circuity in the auditory nerve and cochlear nucleus, and the role of hearing upon their development. These data will have relevance to broader issues in sensory neurobiology and may establish guidelines for cochlear implants in children by defining the time period during which the developing auditory nervous system is most vulnerable to acoustic deprivation.
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