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连接和可塑性中的作用是发育神经科学感兴趣的主要话题。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多的关注。现在大量文献强调了 NMDAR 在神经连接及其可塑性、学习和记忆的发育过程中以及在成熟神经系统病理状态的兴奋性毒性过程中的重要性。该提案的重点是在 NMDAR 功能基因受损的小鼠中开发体感丘脑皮质回路。啮齿动物体感通路是研究体感图中地形连接和图案形成的优秀模型系统。缺乏 NMDAR 关键亚基的小鼠脑干中的体感模式被消除。表达较低水平 NMDAR 功能的小鼠也表现出体感通路中模式的缺失。兴奋性神经元中 NMDAR 受到皮质限制性破坏的小鼠，其体感身体图区域内的皮质模式也表现出严重缺陷。除了轴突和突触后缺陷之外，新皮质内体感身体图的细分也发生了改变。因此，这些小鼠模型提供了一种极好的方法来剖析 NMDAR 在体感身体图的分割以及突触前和突触后神经元件的模式化中的作用。该提案的长期目标是揭示 NMDAR 功能受损后突触后细胞的轴突乔木和树突状过程如何改变。分子遗传学和神经解剖学相结合的方法将用于阐明这些小鼠体感皮层的结构变化。对这种解剖学变化的清晰理解将为剖析哺乳动物感觉通路发育中模式形成和可塑性的分子机制铺平道路。然后，这些研究可以扩展到研究成人皮质可塑性在学习过程中或周围神经损伤的结果的机制。