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. ? ?
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