Synaptic basis for map plasticity in cerebral cortex

描述(由申请人提供)：感觉体验会使大脑皮层回路的功能发生明显的变化，这一过程有助于中风或外周损伤后大脑皮层的发育、学习和功能恢复。这种依赖经验的可塑性背后的细胞机制尚不清楚，也是本应用的主题。这里提出的实验将检验主导假说，即这种可塑性涉及特定皮质突触的快速长时程增强(LTP)和抑制(LTD)，随后是皮质微回路的较慢解剖重组。目前，这一假设依赖于稀少的、往往是间接的证据。这个应用程序建议使用一个强大的模型系统，即大鼠初级躯体感觉(S1)皮质中的胡须图谱，严格检验这一假设。胡须图谱对改变的感觉体验表现出强大的可塑性，但这种可塑性的细胞机制尚不清楚。 通过对动物脑片进行敏感的生理和解剖学测量，将直接检测到皮层可塑性背后的突触变化。在动物脑片中，MAP可塑性是由改变的胡须经验诱导的。这种方法有一个强大的优势，因为可塑性机制是在特定的皮质内突触确定的，因此可以确定这些变化对整体功能可塑性的贡献。本课程将研究突触效能的变化(LTP和LTD)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识别和了解感觉体验自然改变大脑回路和大脑功能的一整套细胞机制。了解这些机制将有助于开发新的药物和行为操作，促进或抑制活着的大脑中特定的可塑性特征。这种手法可能有益于促进学习和改善与可塑性相关的疾病，如智力低下、学习障碍、成瘾和慢性疼痛。此外，这些手法可能会促进中风或外周或脑/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.