Novel sensory experience leads to adaptive functional changes of the adult cortex. Such plasticity underlies important cognitive phenomena, including learning and functional recovery after injury, but the synaptic and circuit basis of plasticity is unknown. We propose to study the mechanisms of adult plasticity in the mouse barrel cortex, at the level of synapses, receptive fields, and neural circuits. Our proposal has four parts: First, we will measure the structural plasticity of axons, dendrites and their spines in vivo using long-term 2-photon imaging in transgenic mice expressing fluorescent proteins. The lifecycle of dendritic spines, and the effects of changing experience, will be mapped throughout the life of the mouse. Second, to relate structural plasticity of spines to synaptic plasticity we will combine in vivo imaging with retrospective serial section electron microscopy. Third, we will use intracellular recording techniques to measure the dynamics of receptive fields in vivo. Experience-dependent changes of synaptic potentials will be compared with plasticity of dendritic spines. Fourth, to discover the circuit elements involved in plasticity we will apply an efficient method for mapping synaptic circuits, laser scanning photostimulation, in brain slices from animals in which sensory experience has been perturbed. Using these mapping techniques we will further address a fundamental question about experience-dependent adult plasticity: are new neural circuits formed, or existing circuits modified? To test the hypothesis that plasticity of synapses, receptive fields, and circuits are different aspects of the same adaptive response, and are causally linked, we will compare their timecourse and circuit loci; we will further use mutant mice (aCaMKII T286A) with deficient experience-dependent receptive field plasticity and analyze their synaptic and circuit plasticity. Our studies will provide an integrated view of the mechanisms of expression underlying experience-dependent plasticity in the adult barrel cortex. Since the microcircuitry and molecular machinery are shared by a wide range of cortices and mammalian species, it is likely that the results from these studies can be generalized to other systems involved in a wide range of cognitive plasticity.
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