Synaptic basis for map plasticity in cerebral cortex

描述（由申请人提供）：感觉体验产生大脑皮层回路功能的充分表征的变化，这是一个有助于大脑皮层发育、学习和中风或外周损伤后功能恢复的过程。这种经验依赖性可塑性的细胞机制尚不清楚，是本申请的主题。这里提出的实验将测试占主导地位的假设，这种可塑性涉及快速长时程增强（LTP）和抑郁症（LTD）的特定皮层突触，其次是较慢的解剖重组皮层微电路。目前，这一假设依赖于稀疏的，往往是间接的证据。本申请提出严格测试这一假设，使用一个强大的模型系统，在大鼠的初级体感（S1）皮层的触须地图。须图显示出强大的可塑性，以改变感官体验，但这种可塑性的细胞机制是未知的。 通过对动物脑切片进行灵敏的生理学和解剖学测量，将直接检测皮层可塑性背后的突触变化，在动物脑切片中，地图可塑性已被改变的胡须经验所诱导。这种方法具有强大的优势，因为可塑性机制是在特定的皮质内突触中识别的，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建。 这项研究的长期目标是确定和理解感觉体验自然改变大脑回路和大脑功能的全套细胞机制。了解这些机制将允许开发新的药理学和行为操纵，促进或抑制活体大脑可塑性的特定功能。这种操作可能有利于促进学习和改善可塑性相关的疾病，如精神发育迟滞，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。

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.