Functional State of Developing Retinogeniculate Synapse

视网膜突触发育的功能状态

• 批准号: 9230839
• 负责人: WILLIAM GUIDO
• 金额: $ 37万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9230839
• 关键词: 3-Dimensional; Address; Adopted; Age; Anatomy; Architecture; Axon; Behavioral; Biological Models; Brain; Brain Stem; Cell Nucleus; Cells; Cholera Toxin Protomer B; Deafferentation procedure; Development; Disease; Dorsal; Electrophysiology (science); Event; Exhibits; Eye; Felis catus; Genetic; Goals; Imagery; In Vitro; Injection of therapeutic agent; Injury; Interneurons; Knowledge; Label; Lateral Geniculate Body; Life; Light; Mus; Neurons; Optic Nerve; Pathway interactions; Pattern; Preparation; Retina; Retinal; Retinal Ganglion Cells; Rhodopsin; Signal Transduction; Slice; Source; Specificity; Synapses; Testing; Thalamic structure; Time; Transgenic Mice; Transgenic Organisms; Trees; Variant; Viral; Visual; Visual Cortex; base; biocytin; cell type; cholinergic; developmental disease; experimental study; field study; insight; loss of function; monocular; mouse model; mutant; nerve supply; nervous system disorder; optogenetics; postnatal; preference; public health relevance; reconstruction; response; retinal axon; retinal progenitor cell; retinogeniculate; synaptogenesis; transcription factor; transmission process

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.

描述（由申请人提供）：我们开发了一种强大的小鼠模型来研究背外侧膝状核（dLGN）的视觉回路发育，即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原化通路以及视网膜神经节细胞和 dLGN 神经元之间连接的细化上。虽然视网膜轴突模式和连接性的许多变化已经被描述，但仍然缺乏有关组织的两个基本方面的信息。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大量输入。这两个方面对于当代对丘脑功能的理解都至关重要，丘脑功能是提供视网膜信号的忠实中继，但同时根据行为状态的变化来调节传输增益。该提案的目标是评估视网膜细化如何与类别特定连接相关，视网膜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，并评估此类输入如何与神经支配协调和细化视网膜原化途径。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，以可视化和实验分离来自视网膜或视觉皮层第六层、丘脑网状核等非视网膜来源的特定细胞类型和脑干胆碱能核。这些研究将 提供有关发育中的大脑如何形成精确的连接模式的有价值的信息，并为研究和治疗因异常连接模式的形成而导致的发育和神经系统疾病提供进一步的见解。