Synaptic basis for map plasticity in cerebral cortex

大脑皮层图谱可塑性的突触基础

• 批准号: 7490770
• 负责人: Daniel Feldman
• 金额: $ 26.95万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490770
• 关键词: Adolescent; Animals; Auditory area; Axon; Behavior Control; Biological Models; Brain; Cells; Cerebral cortex; Chromosome Pairing; DNA Sequence Rearrangement; Data; Dendrites; Development; Disease; Excision; Excitatory Synapse; Exhibits; Injury; Knowledge; Learning; Learning Disabilities; Life; Long-Term Potentiation; Maps; Measurement; Measures; Mental Depression; Mental Retardation; Modification; Neocortex; Neurons; Newborn Animals; Numbers; Pathway interactions; Peripheral; Physiological; Process; Pyramidal Cells; Rattus; Recovery of Function; Rest; Role; Sensory; Shapes; Slice; Specificity; Spinal cord injury; Stroke; Synapses; Techniques; Testing; Vibrissae; Visual; addiction; base; chronic pain; critical developmental period; deprivation; experience; improved; in vivo; novel; reconstruction; research study; response; somatosensory; synaptic depression

DESCRIPTION (provided by applicant): Sensory experience produces well-characterized changes in the function of circuits in the cerebral cortex, a process that contributes to cortical development, learning, and recovery of function after stroke or peripheral injury. The cellular mechanisms underlying such experience-dependent plasticity are not known, and are the subject of this application. The experiments proposed here will test the dominant hypothesis that such plasticity involves rapid long-term potentiation (LTP) and depression (LTD) of specific cortical synapses, followed by slower anatomical reorganization of cortical microcircuitry. Currently, this hypothesis rests on sparse and often indirect evidence. This application proposes to rigorously test this hypothesis using a powerful model system, the whisker map in the rat's primary somatosensory (S1) cortex. The whisker map exhibits robust plasticity in response to altered sensory experience, but the cellular mechanisms for this plasticity are unknown. The synaptic changes underlying cortical plasticity will be detected directly, by making sensitive physiological and anatomical measurements in brain slices prepared from animals in which map plasticity has been induced by altered whisker experience. This approach has a powerful advantage in that plasticity mechanisms are identified at specific intracortical synapses, so the contribution of these changes to overall functional plasticity can be determined. Both changes in synaptic efficacy (LTP and LTD) and anatomical restructuring of neuronal axons and dendrites will be examined. The long-term objective of this study is to identify and understand the full set of cellular mechanisms by which sensory experience naturally alters brain circuits and brain function. Understanding these mechanisms will allow the development of novel pharmacological and behavioral manipulations that promote or inhibit specific features of plasticity in living brains. Such manipulations may be beneficial in promoting learning and in ameliorating plasticity-related disorders such as mental retardation, learning disability, addiction, and chronic pain. In addition, these manipulations may improve recovery of function after stroke or peripheral or brain/spinal cord injury.

描述（由申请人提供）：感官体验会导致大脑皮层回路功能发生明显的变化，这一过程有助于中风或外周损伤后皮层的发育、学习和功能恢复。这种依赖于经验的可塑性背后的细胞机制尚不清楚，并且是本申请的主题。这里提出的实验将检验主要假设，即这种可塑性涉及特定皮质突触的快速长期增强（LTP）和抑制（LTD），随后是皮质微电路的较慢的解剖重组。目前，这一假设依赖于稀疏且往往是间接的证据。该应用程序建议使用强大的模型系统（即大鼠初级体感（S1）皮层中的胡须图）严格测试这一假设。晶须图表现出强大的可塑性来响应感官体验的改变，但这种可塑性的细胞机制尚不清楚。 通过对动物脑切片进行敏感的生理和解剖测量，可以直接检测皮层可塑性背后的突触变化，其中图谱可塑性是由胡须经验改变引起的。这种方法具有强大的优势，因为可以在特定的皮质内突触处识别可塑性机制，因此可以确定这些变化对整体功能可塑性的贡献。将检查突触功效（LTP 和 LTD）的变化以及神经元轴突和树突的解剖结构重组。 这项研究的长期目标是识别和理解感官体验自然改变大脑回路和大脑功能的全套细胞机制。了解这些机制将有助于开发新的药理学和行为操作，以促进或抑制活体大脑可塑性的特定特征。这种操作可能有益于促进学习和改善可塑性相关疾病，例如智力迟钝、学习障碍、成瘾和慢性疼痛。此外，这些操作可以改善中风或外周或脑/脊髓损伤后的功能恢复。