Synaptic basis for map plasticity in cerebral cortex

描述（由申请人提供）：感觉体验在大脑皮层回路功能中产生明显特征的变化，这一过程有助于大脑皮层发育、学习和中风或外周损伤后的功能恢复。这种经验依赖的可塑性背后的细胞机制尚不清楚，是本应用的主题。本文提出的实验将验证主要假设，即这种可塑性涉及特定皮层突触的快速长期增强（LTP）和抑制（LTD），随后是皮层微电路的较慢解剖重组。目前，这一假设建立在稀疏且通常是间接的证据之上。这个应用程序建议使用一个强大的模型系统来严格测试这一假设，即大鼠初级体感（S1）皮层中的须状图。须状图显示出强大的可塑性，以响应改变的感官体验，但这种可塑性的细胞机制尚不清楚。

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.