SOMATOSENSORY CORTICAL DEVELOPMENT AND PLASTICITY

体感皮质发育和可塑性

• 批准号: 6091888
• 负责人: Reha S Erzurumlu
• 金额: $ 16.73万
• 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 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6091888
• 关键词: NMDA receptors; axon; brain stem; dendrites; developmental neurobiology; dorsal column; gene mutation; genetically modified animals; granule cell; immunocytochemistry; laboratory mouse; mammalian embryology; neural plasticity; neuronal transport; somesthetic sensory cortex; thalamus; trigeminal nerve; vibrissae

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.

神经活动在接线和感觉途径的可塑性中的作用是发育神经科学中的一个主要主题。 在过去的十年中，非常关注N-甲基D天冬氨酸（NMDA）受体介导的神经活性的作用。 有大量文献强调了NMDA受体在神经联系的发展及其可塑性，学习和记忆以及在包括灵长类动物在内的许多物种中成熟神经系统的病理状态的兴奋性状态中的重要性。 该提议着重于具有NMDA受体功能的基因操纵的小鼠沿体感途径的神经连接的发展和可塑性。 啮齿动物体感途径是研究体感图内地形连接和图案的出色模型系统。 先前的研究发现，在缺乏NMDA受体的关键亚基的小鼠中，脑干中消除了体感模式。 表达较低水平的NMDA受体功能的小鼠还显示出沿着体感途径的所有图案，从而从面部区域传达信息。 该提案的长期目标是揭示NMDA受体功能受损后，在突触后细胞的轴突乔木和树突状过程等细胞元素如何改变。 分子遗传和神经解剖学的组合将用于阐明沿这些小鼠的体感途径的结构变化。对这种解剖学变化的清晰理解将为开发哺乳动物的感觉途径中的模式形成和可塑性的分子机制铺平道路。