TrkB & Synapse Elimination in the Developing Cerebellum

TrkB

• 批准号: 6998298
• 负责人: Erin M Johnson-Venkatesh
• 金额: $ 4.34万
• 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/6998298
• 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）：本项目的目标是帮助了解中枢神经系统（CMS）中突触功能的发展。我建议专注于调查的成熟的攀爬纤维浦肯野细胞突触和测试的假设，TrkB受体在调节开关从多个到单个的攀爬纤维神经支配的浦肯野细胞在出生后的小脑皮质的发展过程中发挥了作用。为此，我建议调查的时间过程和功能成熟的浦肯野细胞的攀缘纤维神经支配，作为实验模型的转基因小鼠，港口无论是一个hypomorphic水平的TrkB表达或有针对性的删除TrkB在小脑。为了做到这一点，我建议结合联合收割机的行为，神经解剖，分子和电生理的方法，这将为我提供广泛的培训，在智力丰富的环境。我的初步研究结果表明，hypomorphic或TrkB-null小鼠行为共济失调，并显示出持久的多个攀爬纤维神经支配。