Somatosensory Cortical Development and Plasticity

体感皮质发育和可塑性

• 批准号: 7751291
• 负责人: Reha S Erzurumlu
• 金额: $ 32.48万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751291
• 关键词: Adenylate Cyclase; Adult; Area; Axon; Biological Models; Brain; Brain Stem; Cell Nucleus; Cells; Data; Defect; Dendrites; Development; Elements; Face; Funding; Gene Deletion; Genes; Grant; Knock-out; Knockout Mice; Laboratories; Lateral; Learning; Lesion; Literature; Maps; Mediating; Memory; Modeling; Molecular; Molecular Genetics; Mus; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NR1 gene; Neocortex; Neonatal; Nervous system structure; Neuraxis; Neurosciences; Pathway interactions; Pattern; Pattern Formation; Peripheral Nerves; Play; Presynaptic Terminals; Process; Receptor Signaling; Rodent; Role; Sensory; Sensory Deprivation; Signal Transduction; Signaling Molecule; Somatosensory Cortex; Synapses; Testing; Thalamic structure; Time; Vibrissae; barrel cortex; base; body map; critical period; excitatory neuron; excitotoxicity; interest; knock-down; mature animal; mouse model; neural circuit; neural patterning; neurodevelopment; postnatal; postsynaptic; presynaptic; public health relevance; receptor function; receptor-mediated signaling; relating to nervous system; research study; somatosensory; tool

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. A vast body of literature underscores the importance of N-methyl D Aspartate (NMDA) receptor- mediated neural activity 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, somatosensory region-specific knockout mouse models provide an excellent means to dissect out the role of NMDARs and downstream signaling molecules in 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 and thalamus 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. PUBLIC HEALTH RELEVANCE N-methyl D Aspartate (NMDA) receptors (NMDARs) play a major role in development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system. In this proposal we shall test the role of NMDARs in the development and plasticity of somatosensory neural circuits by examining neural defects in NMDAR-deficient mouse models.

描述（由申请人提供）：神经活动在接线和感觉途径可塑性中的作用是发育神经科学感兴趣的主要主题。大量文献强调了N-甲基D天冬氨酸（NMDA）受体介导的神经活动在神经联系的发展及其可塑性，学习和记忆以及成熟神经系统病理状态的兴奋性毒性期间的重要性。该提案的重点是具有遗传损害NMDAR功能的小鼠体感丘脑皮层回路的发展。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。在缺乏NMDAR的关键亚基的小鼠的脑干中，体验模式被废除。表达较低水平的NMDAR功能的小鼠也表明沿着体感途径始终没有图案。兴奋性神经元中NMDAR的皮质限制破坏的小鼠在体感体图区域内还显示出严重的皮质图案缺陷。除了轴突和突触后缺陷外，新皮层内的体感体图的细分也会改变。因此，体感觉区域特异性敲除小鼠模型提供了一种出色的手段，可以剖析NMDAR和下游信号分子在造影前和突触后神经元素中的作用。该建议的长期目标是揭示NMDAR功能受损后，突触后细胞的轴突乔木和树突过程如何改变。结合的分子遗传和神经解剖学方法将用于阐明这些小鼠的体感皮质和丘脑的结构变化。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。然后可以扩展这些研究，以研究学习过程中成人皮质可塑性的机制，或者由于周围神经损伤的结果。公共卫生相关性N-甲基D天冬氨酸（NMDA）受体（NMDAR）在神经联系及其可塑性，学习和记忆以及在成熟神经系统病理状态的兴奋性毒性过程中起着重要作用。在此提案中，我们应通过检查NMDAR缺陷小鼠模型中的神经缺陷来测试NMDAR在体感神经回路的发展和可塑性中的作用。