Experience-Dependent Plasticity Of Synaptic Structure

描述（由申请人提供）：本申请旨在研究突触可塑性的发育调节以及感觉经验在出生后生活中改变神经元连接的作用。利用新开发的体内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，将在长时间内跟踪大脑皮层各个区域单个突触的变化。通过监测树突棘和突触前钮扣的形成、消除和大小变化，研究突触前和突触后结构的可塑性，时间跨度为几周到几个月，动物从青春期进入成年期。此外，体内成像和三维连续电子显微镜的结合将用于研究突触结构变化的超结构相关性。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生活、发育和成熟初级视觉皮层突触连通性的短期和长期影响。这种经验依赖性可塑性的机制将通过可视化突触结构变化来探索，同时操纵n -甲基-d -天冬氨酸（NMDA）受体活性水平。总之，这些研究将提供一个全面的观点，在不同的生命阶段，经验在形成突触连接中的作用，并提出脑损伤后功能康复的潜在策略

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