TrkB & Synapse Elimination in the Developing Cerebellum

TrkB

• 批准号: 7141311
• 负责人: Erin M Johnson-Venkatesh
• 金额: $ 3.41万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141311
• 关键词: brain derived neurotrophic factor; cell line; cerebellar Purkinje cell; cerebellar ataxia /dyskinesia; developmental neurobiology; gene deletion mutation; genetically modified animals; growth factor receptors; innervation; laboratory mouse; predoctoral investigator; protein tyrosine kinase; receptor expression; synaptogenesis; transfection /expression vector; voltage /patch clamp

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.

描述（由申请人提供）：本项目的目标是有助于理解中枢神经系统（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过程，并验证TrkB受体在出生后小脑皮层发育过程中调节浦肯野细胞从多攀爬纤维神经支配向单攀爬纤维神经支配转换的假设。为此，我建议研究攀爬纤维神经的时间进程和功能成熟，使用TrkB在小脑中表达半形态或靶向缺失TrkB的转基因小鼠作为实验模型。为了做到这一点，我建议结合行为学、神经解剖学、分子学和电生理学方法进行研究，这将为我在一个智力丰富的环境中提供广泛的训练。我的初步研究结果表明，hypoomorphic或TrkB-null小鼠是行为共济失调的，并表现出多攀爬纤维神经支配的持久性。