Topographic Maps and Visual Cortical Functions

描述(申请人提供)：视觉空间的视网膜再现是哺乳动物视觉皮质的一般特征。该方案中的实验将研究视网膜定位图是否为感官信息的生理处理所必需。具体地说，这项拟议的工作将研究基因干扰的视网膜定位图对感受野特性、大脑皮层回路和视觉行为的影响。将使用几种在视觉皮质中显示映射错误的突变小鼠，包括缺乏分子指导信号eaffin-as的小鼠，扰乱发育中视网膜自发活动模式的小鼠，以及这两种破坏性干预措施相结合的小鼠。此外，野生型小鼠的视网膜定位图也会因为eparin的错误表达而受到干扰--就像在发育中的视皮层一样。利用这些小鼠，研究人员将首先确定当视网膜定位图被破坏时，皮质感受区是否异常。将进行单个单位的记录，以测量单个皮质神经元的大小、方向选择性和空间调谐。通过比较具有不同程度地图错误的小鼠的感受野特性，将确定地形图在塑造视觉皮质接受野方面的贡献。其次，在没有准确视网膜定位图的情况下，将在完整的大脑中进行细胞内全细胞记录，以研究皮质内突触抑制的模式。最后，使用视觉辨别的游泳测试和视觉运动反应测试，调查人员将确定视网膜地图的中断是否会影响视觉行为。总之，这些研究将阐明视网膜定位图在视觉处理中的作用，并将有助于确定突触连接的准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.