HEARING: DEVELOPMENT OF SYNAPTIC CIRCUITS

描述：本申请将研究提升的发展 在下丘内终止的不重叠或 仅部分重叠的条带和斑块图案。传入束 终止代表垂直偏析横跨厚度的 下丘和斑块的纤维树突层代表了一个 沿着层平面的水平偏析。目前还不知道是否 当传入纤维首先进入下丘脑时， 丘或他们是否形成继发于最初的重叠。 然而，这些传入模式，连同平行的纤维树突 下丘的结构，决定了突触的相互作用 发生在细胞核内。为了了解神经回路 参与信息处理的发展，拟议的研究将确定 1)到达的空间和时间特征，分布和 传入投射的细化，2）这些事件的关系， 突触发生和3）控制模式形成的机制 传入神经终止的机制。具体而言，实验将 通过研究上升预测的发展来解决这些问题 从外侧上级橄榄（LSO）和背侧 高级哺乳动物雪貂的外侧丘系核。的 LSO和DNLL轴突向下投射的位置和分布 丘将在雪貂套件的正常发育系列中进行研究， 一系列耳蜗消融的实验亲脂性碳菁染料， DiI和DiD将用于标记同侧和对侧LSO， DNLL纤维的连合。此外，突触的分布 沿着所述色调轴并平行于所述纤维枝晶层接触 将在跟踪确定的发育时间点采样 问题研究对下丘脑传入投射发育的认识 丘，以及最终形成的整合电路，对于 了解可能由于遗传异常而处于危险中的听觉功能， 营养不平衡，怀孕期间致畸剂的影响，甚至 到早产虽然随后的听觉体验可能会改变内在的 听觉回路，功能回路的最初结构仍然存在 这是理解神经和行为可塑性的基础， 合理干预和治疗效果。

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.