Development of Inhibition in the Avian Cochlear Nucleus

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DESCRIPTION (provided by applicant): The auditory system localizes sound in azimuth by computing interaural time delays. In the avian auditory brainstem, nucleus magnocellularis (NM) is the first central nucleus in this temporal coding pathway. NM contains highly specialized anatomic, synaptic, and intrinsic properties that play key roles in shaping inhibitory responses and maintaining temporal fidelity in NM. The development of these specializations is poorly understood. The first aim is to describe the time-course of the development of inhibition in chick NM using in vitro electrophysiological techniques.. The second aim is to understand the developmental importance of afferent excitatory inputs in the development of inhibition using otocyst removal followed by physiological recordings. The third aim will examine role of Kv1.1 in developing the normal NM phenotype using RNA interference techniques. Plasmids encoding RNAs designed to interfere with the Kcnal, the Kv1.1 gene, and an EGFP reporter gene will be electroporated in ovo in early embryos. The physiology of transfected cells will be examined through development. These manipulations are hypothesized to alter the normal development of NM anatomy and physiological responses to excitatory and inhibitory inputs.