The aim of this proposal is to study the developmental regulation of synaptic plasticity and the role of sensory experience in modifying neuronal connectivity in postnatal life. Using a newly developed in vivo transcranial two-photon imaging technique and transgenic mice expressing Yellow Fluorescent Protein (YFP), changes in individual synapses will be followed over extended periods of time in various regions of the cerebral cortex. The plasticity of pre- and post-synaptic structures will be studied by monitoring the formation, elimination, and change in size of dendritic spines and presynaptic boutons over weeks to months as animals advance from adolescence to adulthood. Furthermore, a combination of in vivo imaging and three-dimensional serial electron microscopy will be used to study the ultra-structural correlates associated with changes in synaptic structures. Because sensory experience can have profound effects on the function of the nervous system, we will determine the short- and long-term influence of visual deprivation on synaptic connectivity in the living, developing and mature primary visual cortex. The mechanisms underlying this experience-dependent plasticity will be explored by visualizing structural changes of synapses while manipulating the level of N-methyI-D-aspartate (NMDA) receptor activity. Together, these studies will provide a comprehensive view of the role of experience in shaping synaptic connectivity at different stages of life and suggest potential strategies for functional rehabilitation after brain injury ? ?
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