Mechanisms of Visual Map Development in the Superior Colliculus

描述(申请人提供)：大脑将有关感官世界的信息组织成地图。突出的例子是外侧膝状核、上丘和视皮层的眼球偏爱和视网膜病变图。这项提议中的实验将促进我们对哺乳动物大脑中负责发展精确神经电路的机制的理解。我们将使用广泛的技术组合，包括体外和体内的分子生物学、细胞生物学和电生理技术。我们的实验集中在小鼠上丘的视觉偏好和视网膜复制图上，这是一种感觉运动结构，已经成为检查神经回路发育和功能的理想模型系统。人们普遍认为，分子线索负责在上丘建立粗略的MAP结构，随后依赖活动的过程将这些感觉运动回路细化到功能精确度。我们建议检查视觉地图开发所必需的活动的性质，并确定这一活动在塑造电路发展方面是允许的还是有指导意义的。我们还建议检查小鼠上丘单个视网膜神经节细胞轴突的正常发育，并确定视网膜活动中断如何扰乱Arbor的发育。最后，我们建议研究上丘调节视觉地图活动依赖细化的突触机制。总而言之，这项提议中的实验旨在研究哺乳动物大脑中负责发展精确神经回路的机制，特别强调小鼠上丘中视觉地图的出现。与公共健康相关：我们有兴趣了解复杂的大脑回路是如何发展的。我们把重点放在视觉系统上，因为人们对它的功能了解得比较清楚，而且它对人类的行为特别重要。我们的实验有可能帮助开发在眼睛创伤或疾病(如青光眼或老年性黄斑变性)后恢复视觉功能的技术。

Description (provided by applicant): The brain organizes information about the sensory world into maps. Prominent examples are the maps of eye-preference and retinotopy in the lateral geniculate nucleus, superior colliculus and visual cortex. Experiments in this proposal will advance our understanding of mechanisms responsible for the development of precise neural circuitry in the mammalian brain. We will use a broad combination of techniques, including molecular biological, cell biological and electrophysiological techniques both in vitro and in vivo. We focus our experiments on maps of eye-preference and retinotopy in the superior colliculus of the mouse, which is a sensory motor structure that has emerged as an ideal model system for the examination of neural circuit development and function. It is widely hypothesized that molecular cues are responsible for the establishment of coarse map structure in the superior colliculus, and activity dependent processes subsequently refine these sensory motor circuits to functional precision. We propose to examine the nature of activity that is necessary for the development of visual maps, and determine whether this activity is permissive or instructive in shaping circuit development. We also propose to examine the normal development of single retinal ganglion cell axon arbors in the superior colliculus of the mouse, and determine how disrupting retinal activity disrupts arbor development. We finally propose to investigate the synaptic mechanisms that mediate activity-dependent refinement of visual maps in the superior colliculus. In all, the experiments in this proposal are designed to investigate the mechanisms responsible for the development of precise neural circuits in the mammalian brain, with a specific emphasis on the emergence of visual maps in the mouse superior colliculus. PUBLIC HEALTH RELEVANCE: We are interested in understanding how complex brain circuits develop. We focus on the visual system, as its function is relatively well understood and it is especially important to human behavior. Our experiments have the potential to help develop techniques to restore visual function following eye trauma or disease, such as glaucoma or age related macular degeneration.