Somatosensory Cortical Development and Plasticity

项目总结：神经活动在感觉的连接和可塑性中的作用 通路是发育神经科学中的一个重要课题。一大堆 文献强调了N-甲基-D-天冬氨酸(NMDA)受体的重要性。 神经连接发育过程中的神经活动及其可塑性， 学习和记忆，以及在病理状态下成熟的兴奋性毒性 神经系统。这项建议的重点是发展体感。 遗传性NMDAR功能受损小鼠的丘脑皮质回路。啮齿动物 体感通路是研究中枢神经系统发育的良好模型系统 体感地图中的地形连接和图案。体感 在缺乏关键亚单位的小鼠脑干中，图案被取消 NMDAR。表达较低水平NMDAR功能的小鼠也表现出缺乏 在整个体感通路上都有图案。大脑皮质受限干扰的小鼠 兴奋性神经元中的NMDAR也显示出严重的皮质图案缺陷 躯体感觉的身体图区域。除了轴突和突触后缺陷， 新大脑皮层内躯体感觉体感图的细分被改变。因此， 体感区域特异性基因敲除小鼠模型提供了一种极好的方法 剖析NMDAR及其下游信号分子在细胞周期调控中的作用 突触前和突触后的神经成分。这项建议的长期目标是 揭示突触后细胞的轴突和树突如何改变 NMDAR功能受损。分子遗传学和神经解剖学相结合 将使用各种方法来阐明躯体感觉皮质的结构变化。 以及这些小鼠的丘脑。对这种解剖学变化的清楚理解将 为剖析花纹形成和可塑性的分子机制铺平道路 在哺乳动物感觉通路的发育过程中。然后，这些研究可以扩展到 探讨成人大脑皮质可塑性在学习过程中或作为结果的机制 周围神经损伤的症状。

Project Summary: The role of neural activity in wiring and plasticity of sensory pathways is a major topic of interest in developmental neuroscience. A vast body of literature underscores the importance of N-methyl D Aspartate (NMDA) receptor- mediated neural activity during development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system. This proposal focuses on the development of somatosensory thalamocortical circuitry in mice with genetically impaired NMDAR function. Rodent somatosensory pathway is an excellent model system to study development of topographic connections and patterning within somatosensory maps. Somatosensory patterns are abolished in the brainstem of mice lacking the critical subunit of the NMDARs. Mice that express lower levels of NMDAR function also show absence of patterning all along the somatosensory pathway. Mice with cortex-restricted disruption of NMDARs in excitatory neurons also display severe defects in cortical patterning within the somatosensory body map region. Aside from axonal and postsynaptic defects, the subdivisions of the somatosensory body map within the neocortex are altered. Thus, somatosensory region-specific knockout mouse models provide an excellent means to dissect out the role of NMDARs and downstream signaling molecules in patterning of pre- and postsynaptic neural elements. The long-term objective of this proposal is to reveal how axon arbors and dendritic processes of postsynaptic cells are altered following impaired NMDAR function. Combined molecular genetic and neuroanatomical approaches will be used to elucidate structural changes in the somatosensory cortex and thalamus of these mice. A clear understanding of such anatomical changes will pave the way for dissecting out molecular mechanisms of pattern formation and plasticity in developing mammalian sensory pathways. These studies could then be expanded to investigate mechanisms of adult cortical plasticity during learning or as a consequence of peripheral nerve damage.