SOMATOSENSORY CORTICAL DEVELOPMENT AND PLASTICITY

神经活动在感觉通路的布线和可塑性中的作用是发育神经科学中的一个重要课题。 在过去的十年中，相当多的注意力集中在N-甲基D天冬氨酸（NMDA）受体介导的神经活动的作用。 有大量文献强调了NMDA受体在神经连接发育及其可塑性、学习和记忆过程中以及在许多物种（包括灵长类动物）的成熟神经系统的病理状态中的兴奋性毒性过程中的重要性。 这项建议的重点是发展和可塑性的神经连接沿着体感通路在小鼠与NMDA受体功能的遗传操作。 啮齿动物躯体感觉通路是研究躯体感觉地图中地形连接和模式化发展的一个很好的模型系统。 先前的研究发现，在缺乏NMDA受体的关键亚基的小鼠中，脑干中的体感模式被废除。 表达较低水平的NMDA受体功能的小鼠也显示出沿着从面部区域传递信息的躯体感觉通路的所有沿着图案的缺乏。 这个建议的长期目标是揭示细胞元素，如轴突乔木和突触后细胞的树突状过程是如何改变受损的NMDA受体功能。 结合分子遗传学和神经解剖学的方法将被用来阐明结构的变化沿着这些小鼠的躯体感觉通路。对这种解剖学变化的清晰理解将为解剖出模式形成和可塑性在哺乳动物感觉通路发育中的分子机制铺平道路。

The role of neural activity in wiring and plasticity of sensory pathways is a major topic of interest in developmental neuroscience. During the past decade, considerable attention is directed toward the role of N-methyl D Aspartate (NMDA) receptor-mediated neural activity. There is a vast body of literature that underscores the importance of NMDA receptors during development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system in many species, including the primates. This proposal focuses on the development and plasticity of neural connections along the somatosensory pathway in mice with genetic manipulations of the NMDA receptor function. Rodent somatosensory pathway is an excellent model system to study development of topographic connections and patterning within somatosensory maps. Previous studies found that in mice lacking the critical subunit of the NMDA receptors, somatosensory patterns are abolished in the brainstem. Mice that express lower levels of NMDA receptor function also show absence of patterning all along the somatosensory pathway conveying information from the face region. The long term objective of this proposal is to reveal how cellular elements such as axon arbors and dendritic processes of postsynaptic cells are altered following impaired NMDA receptor function. A combined molecular genetic and neuroanatomical approach will be used to elucidate structural changes along the somatosensory pathway 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.