TrkB & Synapse Elimination in the Developing Cerebellum

描述(由申请人提供)：本项目的目标是帮助了解中枢神经系统(CMS)突触功能的发展。我建议重点研究攀爬纤维-浦肯野细胞突触的成熟，并验证TrkB受体在小脑皮质出生后发育过程中调节浦肯野细胞从多个攀爬纤维神经支配到单个攀爬纤维神经支配的转换的假设。为此，我建议研究浦肯野细胞攀升纤维神经支配的时间进程和功能成熟，使用在小脑中存在TrkB亚型表达水平或靶向缺失的转基因小鼠作为实验模型。为了做到这一点，我建议进行研究，将行为学、神经解剖学、分子和电生理学方法结合起来，在一个智力丰富的环境中为我提供广泛的训练。我的初步研究结果表明，发育低下或TrkB缺失的小鼠在行为上是共济失调的，并表现出持续的多个攀援纤维神经支配。

DESCRIPTION (provided by applicant): The goal of this project is to contribute to understanding the development of synaptic function in the central nervous system (CMS). I propose to focus on investigating the maturation of the climbing fiber-Purkinje cell synapse and to test the hypothesis that the TrkB receptor plays a role in regulating the switch from multiple to single climbing fiber innervation of Purkinje cells during postnatal development of the cerebellar cortex. To this end, I propose to investigate the time course and functional maturation of climbing fiber innervation of Purkinje cells, using as experimental model transgenic mice that harbor either a hypomorphic level of TrkB expression or a targeted deletion of TrkB in the cerebellum. To do this I propose studies that combine behavioral, neuroanatomical, molecular and electrophysiological approaches that will offer me extensive training in an intellectually rich environment. The results of my preliminary studies suggest that hypomorphic or TrkB-null mice are behaviorally ataxic and show a persistence of multiple climbing fiber innervation.