HEARING: DEVELOPMENT OF SYNAPTIC CIRCUITS

点击翻译按钮获取中文摘要

DESCRIPTION: The present application will study development of ascending projections that terminate within the inferior colliculus in non-overlapping or only partially overlapping patterns of bands and patches. Bands of afferent termination represent a vertical segregation across the thickness of the fibrodendritic layers of the inferior colliculus and patches represent a horizontal segregation along the plane of the layers. It is not known whether these patterns are established as the afferent fibers first enter the inferior colliculus or whether they form secondarily from an initial overlap. Nevertheless these afferent patterns, together with the parallel fibrodendritic architecture of the inferior colliculus, determine the synaptic interactions that take place within the nucleus. In order to understand how neural circuits involved in information processing develop, the proposed studies will identify 1) the spatial and temporal characteristics of arrival, distribution and refinement of afferent projections, 2) the relationship of those events to synaptogenesis and 3) the mechanisms that govern the formation of the pattern of afferent termination within the layers. Specifically, experiments will address these issues by studying the development of the ascending projections to the inferior colliculus from the lateral superior olive (LSO) and dorsal nucleus of the lateral lemniscus (DNLL) in an altricial mammal, the ferret. The position and distribution of the LSO and DNLL axons projecting to the inferior colliculus will be studied in a normal developmental series of ferret kits and an experimental series with cochlear ablations. Lipophilic carbocyanine dyes, DiI and DiD, will be used to label the ipsilateral and contralateral LSO and the commissure of DNLL fibers. In addition, the distribution of synaptic contacts along the tonotopic axis and parallel to the fibrodendritic layers will be sampled at developmental time points determined from the tracing studies. Knowledge of the development of afferent projections to the inferior colliculus, and the integrative circuits that ultimately result, is critical in understanding auditory functions that may be at risk due to genetic anomaly, nutritional imbalance, effects of teratogens during pregnancy or perhaps even to premature birth. While subsequent auditory experience may alter intrinsic auditory circuits, the initial construction of functional circuits remains fundamental to understanding neural and behavioral plasticity that may lead to rational intervention and treatment outcomes.