Mechanisms of Visual Map Development in the Superior Colliculus

描述（由申请人提供）：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体核、上级丘和视觉皮层中的眼睛偏好和视网膜反射图。这项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级丘的眼睛偏好和视网膜反应的地图上，这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，分子线索是负责建立粗地图结构的上级丘，和活动依赖性的过程，随后完善这些感觉运动电路的功能精度。我们建议研究的性质，是必要的视觉地图的发展活动，并确定这种活动是否是许可的或指导性的塑造电路的发展。我们还建议检查正常发展的单一视网膜神经节细胞轴突乔木的上级丘的小鼠，并确定如何破坏视网膜活动破坏乔木的发展。最后，我们建议调查的突触机制，介导的活动依赖性细化的视觉地图的上级丘。总之，本实验旨在研究哺乳动物大脑中精确神经回路的发展机制，特别强调小鼠上级丘中视觉地图的出现。公共卫生相关性：我们有兴趣了解复杂的大脑回路是如何发展的。我们专注于视觉系统，因为它的功能相对较好地理解，它对人类行为特别重要。我们的实验有可能帮助开发技术，以恢复眼外伤或疾病后的视觉功能，如青光眼或年龄相关性黄斑变性。

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.