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

在出生后的发育过程中，哺乳动物皮层中的神经元回路经历了一段时间的完善，在此期间，感官体验导致神经元之间以已经建立的突触为代价形成额外的突触接触。虽然突触后结构在皮质神经元间突触能突触的产生和转换中的作用已被充分理解，但对突触形成和维持的突触前机制知之甚少。我们的研究计划的长期目标是表征突触前结构改变在发育过程中神经元回路的突触重组中的作用，并阐明调节突触前结构可塑性的分子机制。在下一个资助周期，我们将解决SYD-1的哺乳动物直系同源物的作用，SYD-1是一种假定的RhoGT 3激活蛋白（RhoGAP），其特征在于C。elegans和果蝇，在装配和可塑性的突触前专业化。具体来说，我们将

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