Mechanisms of Visual Map Development

描述（由申请人提供）：大脑将视觉世界的信息组织成地图。突出的例子是外侧膝状核、上丘和视觉皮层的视网膜定位图。本提案中的实验将促进我们对视觉地图开发机制的理解。我们将首先测试Sperry的经典化学亲和假设，即投影和靶区的分子双梯度负责视网膜定位图的发展。我们从小鼠上丘获得的初步数据表明，视网膜神经节细胞轴突在到达目标之前存在显著的顺序，当基因操作干扰视网膜切除时，目标前顺序也同样受到干扰。我们将研究正常小鼠和转基因小鼠的预靶排序和视网膜定位图发展的潜在分子机制。人们普遍假设分子线索只负责建立粗略的视网膜病变，而活性依赖过程随后将这种粗略的地形细化到精确。我们将研究视网膜活动的自发波在小鼠上丘视网膜定位图的细化中的作用。我们还将使用体外电生理技术来检查活动依赖机制如何在突触中起作用，以完善视网膜定位图。视觉地图的最终读数是神经元的生理反应。因此，我们将在小鼠上丘进行体内电生理实验，以评估分子和活性依赖因素在视网膜定位图发展中的作用。总之，本提案中的实验旨在研究哺乳动物大脑中视网膜定位图发展的分子和活性依赖机制。

DESCRIPTION (provided by applicant): The brain organizes information about the visual world in maps. Prominent examples are retinotopic maps in the lateral geniculate nucleus, superior colliculus and visual cortex. Experiments in this proposal will advance our understanding of mechanisms for visual map development. We will first test Sperry's classic chemoaffinity hypothesis that dual gradients of molecules in the projection and target fields are responsible for retinotopic map development. Our preliminary data from the superior colliculus of the mouse suggests that there is significant order in retinal ganglion cell axons before they reach their target, and when genetic manipulations disturb retinotopy, pretarget order is similarly disturbed. We will examine potential molecular mechanisms for pretarget ordering and retinotopic map development in normal and transgenic mice. It is widely hypothesized that molecular cues are only responsible for the establishment of coarse retinotopy, and activity dependent processes subsequently refine this coarse topography to precision. We will examine the role of spontaneous waves of retinal activity in the refinement of retinotopic maps in the mouse superior colliculus. We will also use in vitro electrophysiological techniques to examine how activity dependent mechanisms act at the synapse to refine retinotopic maps. The final readout for visual maps is in the physiological response of neurons. We will therefore perform in vivo electrophysiological experiments in mouse superior colliculus to evaluate the role of molecular and activity dependent factors in the development of retinotopic maps. In all, the experiments in this proposal are designed to investigate the molecular and activity dependent mechanisms responsible for the development of retinotopic maps in the mammalian brain.