The role of early postnatal activity in development of physiological properties of neurons and of nuclear organization in the auditory brainstem

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In the developing auditory system, discrete bursts of spontaneous action potentials are generated in the cochlea by ATP-mediated activation of the inner hair cells, and thereafter transferred to the central auditory system. Such bursting activity ceases with the onset of hearing and is believed to play a role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. Recent studies in our lab indicate a facilitating effect of endogenous purinergic signaling on neuronal firing during early postnatal development of specific auditory brainstem neurons. Thus, we hypothesize that the neuronal activity, facilitated by purinergic signaling before hearing onset, plays a specific role in organizing the developing central auditory pathways. Our proposed project will analyze the effects of the rate and the pattern of afferent activity on the physiology and both cellular and nuclear morphology in the cochlear nucleus and in the medial nucleus of the trapezoid body. Two animal models will be used: Pou4f3DTR/+ mice in which cochlear hair cells can be selectively eliminated during early development by injection of diphtheria toxin. Mice lacking purinergic P2X2 and P2X3 receptors (P2X2/P2X3Dbl-/-) will be used as a model to study the impact of altered patterns of afferent activity. The project includes the complementary use of slice- and in vivo electrophysiology. In this way, we can make use of the strengths of either of these two experimental approaches in scrutinizing specific aspects of development.