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.
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