Experience-Dependent Plasticity Of Synaptic Structure

描述(申请人提供)：这项建议的目的是研究突触可塑性的发育调节，以及感觉经验在改变出生后生活中神经元连接方面的作用。利用新开发的活体经颅双光子成像技术和表达黄色荧光蛋白(YFP)的转基因小鼠，将在较长时间内跟踪大脑皮层不同区域单个突触的变化。将通过监测动物从青春期到成年期数周至数月期间树突棘和突触前突触的形成、消除和大小的变化来研究突触前和突触后结构的可塑性。此外，将结合活体成像和三维连续电子显微镜来研究与突触结构变化相关的超结构。由于感觉体验可以对神经系统的功能产生深远的影响，我们将确定视觉剥夺对存活、发育和成熟的初级视皮层突触连接的短期和长期影响。这种经验依赖性可塑性的机制将通过可视化突触的结构变化来探索，同时操纵N-甲基-D-天冬氨酸(NMDA)受体的活性水平。总之，这些研究将提供经验在不同生命阶段在塑造突触连接中的作用的综合观点，并为脑损伤后的功能康复提供潜在的策略建议。

DESCRIPTION (provided by applicant): 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