Topographic Maps and Visual Cortical Functions

描述（由申请人提供）：视觉空间的视网膜定位表征是哺乳动物视觉皮层的一般特征。在这个建议中的实验将研究是否retinotopic地图所需的生理处理的感觉信息。具体来说，拟议的工作将研究遗传破坏视网膜定位图的感受野特性，皮层电路和视觉行为的后果。将使用在其视觉皮层中显示映射错误的几个突变小鼠系，包括缺乏分子引导线索ephrin-As的小鼠，在发育中的视网膜中具有破坏性自发活动模式的小鼠，以及将这两种破坏性干预结合的小鼠。此外，在野生型小鼠中，视网膜定位图也将通过在发育中的视觉皮层中错误表达肝配蛋白-As而被破坏。使用这些小鼠，研究人员将首先确定当视网膜定位图被破坏时，皮层感受野是否异常。将进行单单位记录，以测量单个皮层神经元的大小、方向选择性和空间调谐。通过比较具有不同程度的映射误差的小鼠的感受野特性，将确定地形图在形成视觉皮层中的感受野中的贡献。第二，将在完整脑中进行细胞内全细胞记录，以研究在缺乏精确视网膜定位图的情况下皮质内突触抑制的模式。最后，研究人员将使用视觉辨别的游泳测试和视动反应测试来确定视网膜定位图的破坏是否影响视觉行为。总之，这些研究将阐明视网膜定位图在视觉处理中的作用，也将有助于定义突触连接的精确模式如何有助于神经系统的正常行为输出。重要的是，这些实验将揭示错误连接的视觉系统如何在细胞，电路和行为水平上发挥作用。这些知识将有助于理解和治疗由脑损伤和异常神经元连接引起的疾病。

DESCRIPTION (provided by applicant): Retinotopic representation of visual space is a general feature of mammalian visual cortex. Experiments in this proposal will study whether the retinotopic map is required for the physiological processing of sensory information. Specifically, the proposed work will study the consequences that genetically disrupted retinotopic maps have for receptive field properties, cortical circuits and visual behaviors. Several lines of mutant mice that display mapping errors in their visual cortex will be used, including the mice deficient in the molecular guidance cues ephrin-As, the mice that have disrupted patterns of spontaneous activity in the developing retina, and the mice in which these two disruptive interventions are combined. In addition, retinotopic maps will also be disrupted in wild type mice by misexpressing ephrin-As in the developing visual cortex. Using these mice, the investigators will first determine whether cortical receptive fields are abnormal when retinotopic maps are disrupted. Single-unit recordings will be performed to measure the size, orientation selectivity and spatial tuning of individual cortical neurons. By comparing the receptive field properties of mice that have different degrees of mapping errors, the contribution of topographic maps in shaping receptive fields in the visual cortex will be determined. Second, intracellular whole cell recording will be performed in the intact brain to study the pattern of intracortical synaptic inhibition in the absence of a precise retinotopic map. Finally, using a swimming test of visual discrimination and a test of optomotor response, the investigators will determine whether disruption of retinotopic maps affects visual behaviors. Together, these studies will elucidate the role of retinotopic maps in visual processing and will also help define how precise patterns of synaptic connections contribute to the normal behavioral output of the nervous system in general. Importantly, these experiments will reveal how mis-wired visual systems function at cellular, circuit and behavioral levels. Such knowledge will be useful for the understanding and treatment of disorders resulting from brain injury and from aberrant neuronal connections.