Functional State of Developing Retinogeniculate Synapse

描述(申请人提供)：我们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，dLGN是将视网膜信息传递到视觉皮质的丘脑。到目前为止，研究主要集中在视网膜生成途径和视网膜神经节细胞与dLGN神经元之间联系的改善上。虽然视网膜发生的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RGC和dLGN细胞之间连接的细胞类特异性有关，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的输入。这两个方面对于当代对丘脑功能的理解都是至关重要的，丘脑功能是提供视网膜信号的忠实中继，但同时也基于行为状态的变化来调节传输的增益。该建议的目的是评估视网膜原化精化与类别特异性连接的关系，视网膜原化精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化通路的神经支配和精化相协调。为了解决这些问题，我们将在转基因小鼠身上进行解剖学、电生理学和光遗传学实验，以允许可视化和实验分离来自视网膜或非视网膜来源的特定细胞类型，如视觉皮质VI层、丘脑网状核和脑干胆碱能核。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，并提供对由于形成异常连接模式而导致的发育和神经疾病的研究和治疗的进一步见解。

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.