Mechanisms regulating the structural plasticity of active zone cytomatrices at synapses between cortical neurons

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During postnatal development, neuronal circuits in the mammalian cortex are subject to a period of refinement during which sensory experience leads to the formation of additional synaptic contacts between neurons at the expense of already established synapses. While the role of postsynaptic structures in the generation and turnover of glutamatergic synapses between cortical neurons is well understood, relatively little is known about presynaptic mechanisms contributing to synapse formation and maintenance. The long-term goal of our research program is to characterize the role of presynaptic structural alterations in the synaptic reorganization of neuronal circuits during development and to elucidate the molecular mechanisms regulating presynaptic structural plasticity. In the next grant cycle, we will address the role of mammalian orthologues of SYD-1, a putative RhoGTPase Activating Protein (RhoGAP) characterized in C. elegans and Drosophila, in the assembly and plasticity of presynaptic specializations. Specifically, we will