Functional State of Developing Retinogeniculate Synapse

描述（由申请人提供）：我们已经开发了一个强大的小鼠模型来研究背外侧膝状核（dLGN）的视觉回路发育，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新生通路和视网膜神经节细胞与dLGN神经元之间的连接的细化。虽然视网膜新生轴突模式和连通性的许多变化已经被描绘出来，但关于组织的两个基本方面的信息仍然缺乏。一个与RGCs和dLGN细胞之间连接的细胞类别特异性有关，另一个与dLGN细胞连接的来源有关，即来自非视网膜投射的丰富输入。这两个方面都是当代理解丘脑功能的关键，即提供视网膜信号的忠实中继，同时根据行为状态的变化调节传输的增益。本提案的目标是评估视网膜原环的细化如何与类特异性连接相关，视网膜原环的细化是否以建立可分离的平行视觉通道的方式进行，确定非视网膜投射何时在dLGN中发展，并评估这种输入如何与视网膜原环通路的神经支配和细化相协调。为了解决这些问题，我们将在转基因小鼠中进行解剖、电生理和光遗传学实验，这些实验允许从视网膜或视觉皮层第六层、丘脑网状核和脑干胆碱能核等非视网膜来源中产生的特定细胞类型的可视化和实验分离。这些研究将

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.