Functional State of Developing Retinogeniculate Synapse

描述（由申请人提供）：我们已经开发了一种强大的小鼠模型来研究背外侧膝状体核（dLGN）中的视觉回路发育，dLGN是视网膜信息到视觉皮层的丘脑中继。迄今为止，研究主要集中在视网膜神经节细胞和dLGN神经元之间的连接的retinogeniculate途径和细化。虽然许多的变化retinogeniculate轴突的图案和连接已经划定，有关组织的两个基本方面的信息仍然缺乏。一个涉及RGC和dLGN细胞之间连接的细胞类别特异性，另一个涉及与dLGN细胞连接的来源，即来自非视网膜投射的大量输入。这两个方面对于当代理解丘脑功能至关重要，丘脑功能提供视网膜信号的忠实中继，但同时根据行为状态的变化调节传输增益。这个建议的目标是评估retinogeniculate细化涉及到类特定的连接，是否retinogeniculate细化的方式，建立可分离的平行视觉通道，以确定何时在dLGN的非视网膜投影发展，并评估如何输入协调与神经支配和细化的retinogeniculate通路。为了解决这些问题，我们将在转基因小鼠中进行解剖学，电生理学和光遗传学实验，这些实验允许从视网膜或从视觉皮层的第VI层，丘脑网状核和脑干胆碱能核等非视网膜来源产生的特定细胞类型的可视化和实验分离。这些研究将 提供关于发育中的大脑如何形成精确的连接模式的有价值的信息，并为研究和治疗由异常连接模式形成引起的发育和神经系统疾病提供进一步的见解。

DESCRIPTION (provided by applicant): We have developed a powerful mouse model to study visual circuit development in the dorsal lateral geniculate nucleus (dLGN), the thalamic relay of retinal information to the visual cortex. To date, studies have focused largely on the retinogeniculate pathway and the refinement of connections between retinal ganglion cells and dLGN neurons. While many of the changes in retinogeniculate axon patterning and connectivity have been delineated, information about two fundamental aspects of organization is still lacking. One relates to the cell- class specificity of connections between RGCs and dLGN cells and the other pertains to the source of connections to dLGN cells, namely the wealth of input that arises from nonretinal projections. Both aspects are critical for a contemporary understanding of thalamic function, which is to provide a faithful relay of retinal signals but at the same time to modulate the gain of transmission based on changes in behavioral state. The goals of this proposal are to assess how retinogeniculate refinement relates to class specific connections, whether retinogeniculate refinement proceeds in a way that establishes separable parallel visual channels, to determine when nonretinal projections develop in dLGN, and to assess how such input coordinates with the innervation and refinement of the retinogeniculate pathway. To address these issues, we will conduct anatomical, electrophysiological, and optogenetic experiments in transgenic mice that allow for the visualization and experimental isolation of specific cell types arising from the retina or from such nonretinal sources as layer VI of visual cortex, the thalamic reticular nucleus, and cholinergic nuclei of the brainstem. These studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity.