Identifying genes that maintain stable neural activity

描述（由申请人提供）：神经系统中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知之甚少。最近的研究表明，稳态机制监测和调节神经系统中细胞兴奋的水平。在果蝇中的神经元兴奋性的稳态调节的模型已经开发出在突触能突触中，其与脊椎动物中枢和外周神经系统中的突触稳态的模型平行。这个提议详细描述了旨在阐明果蝇突触稳态特性的实验。这一办法将是双重的。首先，将进行电生理技术来表征突触稳态的时程和可逆性。为此，将使用GAL 4-UAS系统，其将允许肌肉兴奋的条件性破坏，并且因此允许稳态信号传导的条件性激活。其次，将进行基因组规模的反向遗传学筛选，以鉴定参与稳态信号传导的基因。为了进行该筛选，可获得7260个果蝇dsRNA分子的文库。

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.