SOMATOSENSORY CORTICAL DEVELOPMENT AND PLASTICITY

神经活动在感觉通路的连接和可塑性中的作用是发育神经科学中感兴趣的一个主要主题。在过去的十年中，N-甲基-D-天冬氨酸(NMDA)受体介导的神经活动的作用受到了相当大的关注。有大量的文献强调NMDA受体在神经连接的发育及其可塑性、学习和记忆中的重要性，以及在包括灵长类在内的许多物种成熟神经系统的病理状态下的兴奋毒性过程中的重要性。这项建议侧重于通过基因操作NMDA受体功能的小鼠躯体感觉通路上神经连接的发展和可塑性。啮齿动物体感通路是研究体感地形图中的地形图连接和图形发展的一个很好的模型系统。先前的研究发现，在缺乏NMDA受体关键亚单位的小鼠中，脑干中的体感模式被取消。表达较低水平NMDA受体功能的小鼠也显示出在从面部区域传递信息的躯体感觉通路上一直缺乏图案。这一提议的长期目标是揭示NMDA受体功能受损后突触后细胞成分如轴突和树突是如何改变的。将使用分子遗传学和神经解剖学相结合的方法来阐明这些小鼠躯体感觉通路上的结构变化。对这些解剖学变化的清楚理解将为剖析哺乳动物发育中感觉通路的模式形成和可塑性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.