Somatosensory Cortical Development and Plasticity

体感皮质发育和可塑性

• 批准号: 6776289
• 负责人: Reha S Erzurumlu
• 金额: $ 32.14万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6776289
• 关键词: NMDA receptors; brain mapping; brain morphology; cell death; cell differentiation; dendrites; developmental neurobiology; excitatory aminoacid; gene targeting; genetic techniques; genetically modified animals; immunocytochemistry; laboratory mouse; molecular genetics; neural plasticity; neuroanatomy; receptor expression; somesthetic sensory cortex; synapses; thalamocortical tract

DESCRIPTION (provided by applicant): 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. A vast body of literature now underscores the importance of NMDARs 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, these mouse models provide an excellent means to dissect out the role of NMDARs in parcellation of somatosensory body maps, and 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 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.

描述（由申请人提供）：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的主要研究课题。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。大量的文献强调了NMDAR在神经连接发育及其可塑性、学习和记忆过程中以及在成熟神经系统病理状态下的兴奋性毒性过程中的重要性。这项建议的重点是发展的体感丘脑皮层电路的小鼠与遗传受损的NMDAR功能。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。在缺乏NMDAR关键亚基的小鼠脑干中，体感模式被消除。表达较低水平的NMDAR功能的小鼠也显示出沿着躯体感觉通路的所有沿着图案的缺乏。在兴奋性神经元中具有NMDAR的皮质限制性破坏的小鼠也在躯体感觉身体地图区域内的皮质图案化中显示严重缺陷。除了轴突和突触后缺陷外，新皮层内躯体感觉体地图的细分也发生了改变。因此，这些小鼠模型提供了一个很好的手段来解剖出的作用，NMDAR的躯体感觉身体地图的包裹，和模式化的前和突触后神经元。这项建议的长期目标是揭示突触后细胞的轴突乔木和树突状过程是如何改变受损的NMDAR功能。结合分子遗传学和神经解剖学的方法将被用来阐明这些小鼠的躯体感觉皮层的结构变化。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。这些研究可以扩展到研究学习过程中或周围神经损伤后成人皮质可塑性的机制。