This proposal examines two topics: (1) Spontaneous action potential discharge in the developing auditory system. (2) Regeneration of cochlear hair cells. 1. The spontaneous discharge of neurons in the magnocellular (NM) and laminar (NL) nuclei of the chick occurs in a synchronously rhythmic pattern during the embryonic development of hearing but not after hatching. The characteristics of this synchronously rhythmic pattern of discharge will be examined in recordings of single and multiple unit activity from NM in embryos. The relative amount of synchrony in spontaneous discharge between different tonotopic regions of NM will be measured quantitatively. The overall objective is to understand the contribution of spontaneous activity to the development of auditory system structure and function. 2. Hair cells in the avian cochlea which are lost following injury are replaced by the regeneration of new hair cells. Experiments will examine the restoration of physiological function following hair cell regeneration. Hair cell loss will be induced in birds by injections of gentamicin, an aminoglycoside antibiotic. In the first experiment, auditory thresholds and compound action potential tuning curves will be measured in birds at various post-injection survival intervals. Measurements of the number of cochlear hair cells and ganglion neurons in these birds will allow loss and recovery of physiological function to be related to structural changes. In the second experiment, the tonotopic organization of NM and NL will be measured physiologically at different intervals following gentamicin treatment. The goal of these studies is to understand the mechanisms of hair cell regeneration and the potential for restoration of hearing and normal physiological function.
