Mechanisms of Visual Map Development in the Thalamus and 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。我们将采用广泛的技术，包括分子生物学，细胞生物学，神经解剖学，电生理学和先进的光学成像技术在体外和体内。我们的实验集中在小鼠的上级丘和外侧膝状体核的眼睛偏好和视网膜反应的地图。这些结构是视网膜投射到大脑的主要目标。外侧膝状体核是视觉信息到视皮层的主要中继，而上级丘是感觉运动结构，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糙的地图结构，在外侧膝状体和上级丘，和活动依赖的过程，随后完善这些感觉运动电路的功能精度。我们首先建议明确建立模式化的自发活动是否是必要的视觉地图的发展。接下来，我们建议操纵在发育中的视网膜的活动的时间模式，以检查视网膜神经节细胞活动的视网膜丘发育的依赖性。最后，我们建议操纵的空间模式的活动在发展中的视网膜检查依赖的视觉地图发展的空间特征的自发视网膜活动。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。

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 employ a broad range of techniques, including molecular biological, cell biological, neuroanatomical, electrophysiological and advanced optical imaging techniques in vitro and in vivo. We focus our experiments on maps of eye preference and retinotopy in the superior colliculus and lateral geniculate nucleus of the mouse. These structures are the dominant target of retinal projections to the brain. The lateral geniculate nucleus is the primary relay of visual information to the visual cortex, and the superior colliculu 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 lateral geniculate and superior colliculus, and activity dependent processes subsequently refine these sensory motor circuits to functional precision. We first propose to definitively establish whether patterned spontaneous activity is necessary for the development of visual maps. We next propose to manipulate the temporal pattern of activity in the developing retina to examine the dependence of retinocollicular development of retinal ganglion cell activity. We finally propose to manipulate th spatial pattern of activity in the developing retina to examine the dependence of visual map development on the spatial character of spontaneous retinal activity. 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.