Identifying genes that maintain stable neural activity

识别维持稳定神经活动的基因

• 批准号: 6946808
• 负责人: CARL ANDREW FRANK
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946808
• 关键词: Drosophilidae; biological signal transduction; biotechnology; developmental neurobiology; double stranded RNA; electrophysiology; gene expression; genetic library; genetic regulation; genetic screening; genetically modified animals; green fluorescent proteins; homeostasis; in situ hybridization; neural plasticity; neural transmission; neuromuscular junction; neurons; neurophysiology; postdoctoral investigator; protein localization; synapses

DESCRIPTION (provided by applicant): The balance of excitation and inhibition in the nervous system appears to be a key factor in the etiology of many neurodegenerative diseases. However, the mechanisms that control this balance are poorly understood. Recent studies suggest that homeostatic mechanisms monitor and regulate the levels of cellular excitation in the nervous system. A model for the homeostatic regulation of neuronal excitability has been developed at a glutamatergic synapse in Drosophila that parallels models of synaptic homeostasis in the vertebrate central and peripheral nervous systems. This proposal details experiments designed to elucidate the properties of synaptic homeostasis in Drosophila. The approach will be twofold. First, electrophysiological techniques will be conducted to characterize the time-course and reversibility of synaptic homeostasis. To do this, the GAL4-UAS system will be used, which will allow conditional disruption of muscle excitation, and therefore, conditional activation of homeostatic signaling. Second, a genome-scale, reverse genetics screen to identify genes involved in homeostatic signaling will be performed. To conduct this screen, a library of 7260 Drosophila dsRNA molecules is available.

描述（由申请人提供）：神经系统兴奋和抑制的平衡似乎是许多神经退行性疾病病因学的关键因素。然而，控制这种平衡的机制却知之甚少。最近的研究表明，体内平衡机制监测和调节神经系统中细胞兴奋的水平。在果蝇的谷氨酸能突触中建立了一个神经元兴奋性的稳态调节模型，该模型与脊椎动物中枢和周围神经系统的突触稳态模型相似。本文详细介绍了旨在阐明果蝇突触稳态特性的实验。这种方法将是双重的。首先，电生理技术将用于表征突触内稳态的时间过程和可逆性。为此，将使用GAL4-UAS系统，该系统将允许有条件地中断肌肉兴奋，从而有条件地激活稳态信号。其次，将进行基因组规模的反向遗传学筛选，以确定参与稳态信号传导的基因。为了进行这项筛选，一个包含7260个果蝇dsRNA分子的文库是可用的。