Molecular Neurobiology of Behavioral Rhythms

行为节律的分子神经生物学

基本信息

批准号：
7008515
负责人：
JEFFREY C HALL
金额：
$ 22.59万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-01 至 2008-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Experiments are proposed to delve into the cellular neurobiology of Drosophila's rhythm system--the cells, molecules, and systems that underlie the animal's rest-activity cycles. One focus will involve certain adult-brain neurons, within which actions of and interactions among clock-gene products are hypothesized to form the molecular and cellular substrates of circadian behavioral rhythms: How do these proteins physically interact in vivo? To this end, FRET-based analyses will be performed to assess such biologically meaningful interactions. This will complement and may even modify the conventional view of clockwork protein-protein interactions, because the latter stems largely from characterizations of the protein interactions in tissue extracts or cultured non-neuronal cells. In experiments to be carried out at more of a systems level, THE FUNCTIONS [sic] of the brain neurons in question will be dissected by manipulations of transgenes derived from in-hand clock genes, and from the identification of others by virtue of their presumed specification of pacemaker-output factors. Which subsets of these neurons carry out functions that are output into rhythmic behavior per se, and which are involved in communication among cells within the pacemaking system? Do the presumed neurochemical outputs (alluded to above) function in that manner only, or do they also mediate feedback functions back into the pacemakers (considered both cellularly and molecularly)? With regard to the known rhythmic oscillations of certain clock-gene products and putative clock-output molecules--which of these systematic fluctuations are important for the behavioral rhythmicity that can be sustained in constant environmental conditions, and is such molecular maintenance in part a systems property (involving interactions among certain neurons, cellular feedback phenomena, or both)? Daily oscillations of behavior in Drosophila represent a feature of circadian rhythmicity that is among the most prominent and widespread among metazoan organisms. Moreover, the kinds of gene products and the ways they form the clockworks are analogous across a broad array of species. Therefore, brain-behavior studies of chronobiology in this model system may provide insights into the nature of certain rhythm-related disorders of humans, some of which are associated with genetic variations of Drosophila clock gene orthologs

描述（由申请人提供）：提出了实验来研究果蝇节律系统的细胞神经生物学 - 细胞，分子和系统，这些细胞，分子和系统是动物静止活性周期的基础。一个重点将涉及某些成人脑神经元，其中假设时钟基因产物之间的作用和相互作用形成昼夜节律行为节奏的分子和细胞底物：这些蛋白如何在体内物理相互作用？为此，将进行基于FRET的分析以评估这种具有生物学意义的相互作用。这将补充，甚至可以改变发条蛋白 - 蛋白质相互作用的常规视图，因为后者在很大程度上源于组织提取物或培养的非神经元细胞中蛋白质相互作用的特征。在更多的系统级别进行的实验中，所讨论的脑神经元的功能[SIC]将通过源自手中的基因的转基因的操纵以及其他人的鉴定，从而通过其推测的Pacemaker-actup-utput因子的规范来解剖。这些神经元的哪些子集具有输出为节奏行为本身的功能，哪些与起搏系统中细胞之间的通信有关？假定的神经化学输出（所指上述）是否仅以这种方式函数，还是它们还会介导反馈功能回到起搏器中（均和分子视为）？关于某些时钟基因产品和推定的时钟输出分子的已知节奏振荡 - 这些系统的波动中，其中可以在持续的环境条件下可以维持的行为节奏重要，并且在某些神经元，蜂窝反馈景色或两者之间的相互作用中是在持续的环境条件下维持的，或者是一种分子维护吗？果蝇行为的每日振荡代表了昼夜节律的特征，这是后生生物中最杰出和最广泛的节奏之一。此外，基因产物及其形成发条的方式在各种各样的物种中都是类似的。因此，在该模型系统中对年级生物学的脑行为研究可能会提供有关人类某些与节律相关性疾病的性质的见解，其中一些与果蝇的遗传变异有关