Synaptic Refinement in the Thalamus

丘脑突触细化

• 批准号: 8469102
• 负责人: Zhong-Wei Zhang
• 金额: $ 36万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469102
• 关键词: Acute; Adult; Animals; Anxiety Disorders; Autistic Disorder; Behavior; Brain; Brain Diseases; Cells; Complex; Development; Disease; Electron Microscopy; Environment; Epilepsy; Genes; Genetic; Goals; Health; Heterogeneity; Learning; Life; Mediating; Memory; Modeling; Molecular; Mood Disorders; Mus; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neuronal Injury; Neuronal Plasticity; Neurons; Newborn Infant; Pathway interactions; Pharmacology; Play; Preparation; Process; Property; Regulation; Research; Role; Schizophrenia; Sensory; Sensory Deprivation; Slice; Synapses; System; Thalamic structure; Vibrissae; base; critical period; deprivation; early experience; experience; genetic analysis; improved; information processing; insight; light microscopy; mature animal; nerve injury; nervous system development; neural circuit; novel; patch clamp; response; somatosensory; transmission process

DESCRIPTION (provided by applicant): The refinement of neuronal connections, which consists of selective elimination and consolidation of synapses, is a key mechanism of neuroplasticity. Disruptions of this process, caused by either environmental or genetic factors or both, are thought to be a substrate for altered information processing and abnormal behaviors associated with common developmental brain disorders including autism and schizophrenia. Mechanisms underlying synaptic refinement during development may also be involved in plasticity in the adult brain associated with learning, memory, and neuronal injuries. The long-term goal of this research is to understand how neurons in immature brains selectively eliminate some synapses while reinforcing others. We use sensory relay synapses in the thalamus of the mouse as a model to investigate the cellular and molecular mechanisms underlying synaptic refinement. We will use a novel slice preparation to quantitatively analyze the number and properties of synapses at the single-cell level in whisker sensory relay neurons in the thalamus of normal and genetically modified mice. We will determine the structural basis of synaptic refinement through quantitative analyses of the synapse using light and electron microscopy. Specific Aim 1 proposes to analyze the effects of sensory deprivation and identify the underlying cellular and molecular mechanisms. We hypothesize that sensory experience plays a critical role in developmental refinement of the synapse. Specific Aim 2 proposes to investigate the roles of NMDA (N-methyl-D-aspartate) receptor subunits NR2A and NR2C at this synapse. We hypothesize that the developmental switch of NMDA receptor composition plays an important role in synaptic refinement.

描述（由申请人提供）：神经元连接的细化包括突触的选择性消除和巩固，是神经可塑性的关键机制。由环境或遗传因素或两者共同引起的这一过程的破坏被认为是信息处理改变和与常见发育性脑部疾病（包括自闭症和精神分裂症）相关的异常行为的基础。发育过程中突触细化的潜在机制也可能涉及与学习、记忆和神经元损伤相关的成人大脑的可塑性。这项研究的长期目标是了解未成熟大脑中的神经元如何选择性地消除一些突触，同时增强其他突触。我们使用小鼠丘脑中的感觉中继突触作为模型来研究突触细化背后的细胞和分子机制。我们将使用一种新型切片制剂来定量分析正常和转基因小鼠丘脑胡须感觉中继神经元的单细胞水平突触的数量和特性。我们将通过使用光学和电子显微镜对突触进行定量分析来确定突触细化的结构基础。具体目标 1 建议分析感觉剥夺的影响并确定潜在的细胞和分子机制。我们假设感觉体验在突触的发育细化中起着至关重要的作用。具体目标 2 建议研究 NMDA（N-甲基-D-天冬氨酸）受体亚基 NR2A 和 NR2C 在该突触中的作用。我们假设 NMDA 受体组成的发育转换在突触细化中发挥重要作用。