Mechanisms of Visual Map Development in the Superior Colliculus

描述（由申请人提供）：大脑将感官世界的信息组织成地图。突出的例子是外侧膝状核、上丘和视觉皮层的眼睛偏好图和视网膜切除图。这一提议中的实验将促进我们对哺乳动物大脑中精确神经回路发展机制的理解。我们将在体外和体内使用广泛的技术组合，包括分子生物学，细胞生物学和电生理学技术。我们将实验重点放在小鼠上丘的眼偏好图和视网膜切除图上，上丘是一种感觉运动结构，已成为检查神经回路发育和功能的理想模型系统。人们普遍假设，分子线索负责在上丘中建立粗糙的地图结构，活动依赖过程随后将这些感觉运动电路细化到功能精确。我们建议检查视觉地图发展所必需的活动的性质，并确定这种活动在形成回路发展方面是允许的还是有益的。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，并确定破坏视网膜活动如何破坏树突发育。我们最后建议研究突触机制，调解活动依赖的视觉地图细化在上丘。总之，本提案中的实验旨在研究哺乳动物大脑中精确神经回路发展的机制，特别强调小鼠上丘中视觉地图的出现。公共卫生相关性：我们对了解复杂的大脑回路是如何发展的很感兴趣。我们关注的是视觉系统，因为它的功能相对来说已经被很好地理解了，而且它对人类行为尤其重要。我们的实验有潜力帮助开发在眼外伤或疾病（如青光眼或年龄相关性黄斑变性）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.