Mechanisms of Visual Map Development

描述（由申请人提供）：大脑在地图中组织有关视觉世界的信息。突出的例子是外侧膝状体核、上级丘和视觉皮层中的视网膜定位图。在这个建议中的实验将促进我们的理解机制的视觉地图的发展。我们将首先测试斯佩里的经典chemoaffinity假说，双梯度的分子在投影和目标领域负责retinotopic地图的发展。我们的初步数据从上级丘的小鼠表明，有显着的顺序在视网膜神经节细胞轴突之前，他们到达他们的目标，当遗传操作干扰retinotopy，pretarget秩序同样受到干扰。我们将研究在正常和转基因小鼠中前靶点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糙的视网膜，和活动依赖性的过程，随后完善这个粗糙的地形精确。我们将研究视网膜活动的自发波在小鼠上级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研究活动依赖机制如何在突触处起作用，以改进视网膜定位图。视觉地图的最终读数是神经元的生理反应。因此，我们将在小鼠上级丘进行体内电生理实验，以评估分子和活性依赖因子在视网膜定位图发展中的作用。总之，本实验旨在研究哺乳动物脑中视网膜定位图形成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.