Glial Cell Regulation of Circadian Behavior

神经胶质细胞对昼夜节律行为的调节

基本信息

  • 批准号:
    8131930
  • 负责人:
  • 金额:
    $ 35.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-09-01 至 2015-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The human brain contains more than 100 billion cells, the majority being non-excitable glial cells. Recent studies, including those from the applicant's lab, demonstrate that glial cells of vertebrate and invertebrate nervous systems have remarkably dynamic roles in the regulation of physiological and behavioral processes. Studies in mammals have demonstrated that neurons and glia communicate with one another and this has given rise to a model of the "tripartite synapse" wherein a glial cell (an astrocyte) cooperates with presynaptic and postsynaptic neuronal elements to regulate communication events and behavioral processes (see Significance). Recent studies from the applicant's lab describe a role for a defined population of Drosophila astrocytes in the regulation of circadian behavior. Other studies have documented additional functions for fly glia in the regulation of neurotransmission and behavior (reviewed in Jackson and Haydon, 2008). In the present application, we propose experiments to elucidate the functions of glia in circadian timing. Our studies will employ Drosophila so as to be able to utilize sophisticated genetic techniques to study neuron-glia interactions in the circadian system. The work will utilize innovative genetic, behavioral, imaging and electrophysiological approaches and, importantly, the PI and co-I have complementary strengths in these areas. We propose three specific aims that will test explicit hypotheses about neuron-glia interactions in the circadian system: (1) Test the hypothesis that gliotransmission or other glial processes are essential for circadian behavior; (2) Test the hypothesis that glia regulate pacemaker neurons; and (3) Test the hypothesis that clock neurons regulate glial rhythms. We expect that the results of these studies will highlight general mechanisms by which neurons and glia cooperate to influence circadian rhythmicity and other behaviors. In most neurological disorders and psychiatric states, glial cell gene expression profiles are altered, and it is likely that this initiates dramatic structural/functional changes in the brain that lead to these disorders. Alterations of glial cell biology have been implicated in mental and neurodegenerative diseases including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), schizophrenia, epilepsy, and Alzheimer's. Our proposed studies of glia and circadian control mechanisms have considerable significance for an understanding of pathophysiological conditions such as jetlag and sleep/wake disorders resulting from environmental or genetic perturbations of the circadian system. Molecular components of the circadian system are conserved between insects and mammals, including humans, and Drosophila is an outstanding model for conducting genetic investigations of circadian behavior. It is anticipated that the results of our proposed studies will provide important and general insights about the interaction of glia with the neuronal circuitry controlling behavior, insights which are critical for understanding the roles of glial cells in health and disease. PUBLIC HEALTH RELEVANCE: The human brain contains more than 100 billion cells, the majority being non-excitable glial cells; we propose studies that will utilize behavioral measures, imaging technology and other neurobiological methods to understand communication between neurons and glia of the adult nervous system. The model we propose to use for understanding neuron-glia communication is the circadian clock system as much is known about the neural circuitry responsible for circadian behavior. Our proposed studies have significance for understanding the roles of glia and neuron-glia communication in health and many different neurological diseases.
描述(申请人提供):人脑包含超过1000亿个细胞,其中大部分是不可兴奋的神经胶质细胞。最近的研究,包括申请人实验室的研究,表明脊椎动物和无脊椎动物神经系统的神经胶质细胞在调节生理和行为过程中具有显著的动态作用。在哺乳动物中的研究表明,神经元和神经胶质细胞相互通信,这产生了一种“三方突触”模型,在这种模型中,神经胶质细胞(星形胶质细胞)与突触前和突触后的神经元元件合作,调节通信事件和行为过程(见重要性)。申请人实验室最近的研究描述了一定数量的果蝇星形胶质细胞在调节昼夜节律行为中的作用。其他研究已经证明了苍蝇胶质细胞在调节神经传递和行为方面的额外功能(在杰克逊和海登2008年发表的评论中)。在目前的应用中,我们建议通过实验来阐明神经胶质细胞在昼夜节律中的功能。我们的研究将使用果蝇,以便能够利用复杂的遗传技术来研究昼夜节律系统中神经元-神经胶质细胞的相互作用。这项工作将利用创新的遗传、行为、成像和电生理方法,重要的是,PI和co-I在这些领域具有互补优势。我们提出了三个具体的目标来测试关于昼夜节律系统中神经元-胶质细胞相互作用的明确假设:(1)测试神经胶质传递或其他神经胶质过程对昼夜行为至关重要的假设;(2)测试神经胶质细胞调节起搏器神经元的假设;以及(3)测试时钟神经元调节神经胶质节律的假设。我们希望这些研究的结果将突出神经元和神经胶质细胞合作影响昼夜节律和其他行为的一般机制。在大多数神经疾病和精神状态中,神经胶质细胞的基因表达谱会改变,这可能会引发大脑结构/功能的戏剧性变化,从而导致这些疾病。神经胶质细胞生物学的改变涉及精神和神经退行性疾病,包括多发性硬化症(MS)、肌萎缩侧索硬化症(ALS)、精神分裂症、癫痫和阿尔茨海默氏症。我们提出的神经胶质细胞和昼夜节律控制机制的研究对于理解时差和睡眠/觉醒障碍等病理生理状况具有重要意义,这些疾病是由环境或遗传的昼夜节律扰动引起的。昼夜节律系统的分子组成在昆虫和哺乳动物之间是保守的,包括人类,果蝇是进行昼夜行为遗传研究的杰出模型。预计我们建议的研究结果将提供关于神经胶质细胞与控制行为的神经回路相互作用的重要和一般性的见解,这些见解对于理解胶质细胞在健康和疾病中的作用至关重要。 与公共健康相关:人脑包含超过1000亿个细胞,其中大部分是不可兴奋的神经胶质细胞;我们提出的研究将利用行为测量、成像技术和其他神经生物学方法来了解成人神经系统神经元和神经胶质之间的通信。我们建议用来理解神经元-神经胶质细胞通讯的模型是昼夜节律时钟系统,因为我们对负责昼夜行为的神经回路已经有了很多了解。我们提出的研究对于理解神经胶质细胞和神经元-神经胶质细胞通讯在健康和许多不同神经系统疾病中的作用具有重要意义。

项目成果

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F Rob JACKSON其他文献

F Rob JACKSON的其他文献

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{{ truncateString('F Rob JACKSON', 18)}}的其他基金

Secreted astrocyte proteins regulating rhythmic behavior
分泌的星形胶质细胞蛋白调节节律行为
  • 批准号:
    10178780
  • 财政年份:
    2021
  • 资助金额:
    $ 35.37万
  • 项目类别:
Astrocyte modulation of sleep
星形胶质细胞对睡眠的调节
  • 批准号:
    9977360
  • 财政年份:
    2020
  • 资助金额:
    $ 35.37万
  • 项目类别:
Roles of a novel immunoglobulin-domain protein in sleep and circadian behavior
新型免疫球蛋白结构域蛋白在睡眠和昼夜节律行为中的作用
  • 批准号:
    9095569
  • 财政年份:
    2016
  • 资助金额:
    $ 35.37万
  • 项目类别:
ELECTROPHYSIOLOGY - TUSM/T-NEMC CENTER FOR NEUROSCIENCE RESEARCH
电生理学 - TUSM/T-NEMC 神经科学研究中心
  • 批准号:
    8787523
  • 财政年份:
    2014
  • 资助金额:
    $ 35.37万
  • 项目类别:
Genetic Analysis of Glia-to-Neuron Communication
胶质细胞与神经元通讯的遗传分析
  • 批准号:
    8374352
  • 财政年份:
    2012
  • 资助金额:
    $ 35.37万
  • 项目类别:
Regulation of Astrocyte Heterogeneity and Developmental Maturation in the CNS
中枢神经系统星形胶质细胞异质性和发育成熟的调节
  • 批准号:
    8440943
  • 财政年份:
    2012
  • 资助金额:
    $ 35.37万
  • 项目类别:
Regulation of Astrocyte Heterogeneity and Developmental Maturation in the CNS
中枢神经系统星形胶质细胞异质性和发育成熟的调节
  • 批准号:
    8599794
  • 财政年份:
    2012
  • 资助金额:
    $ 35.37万
  • 项目类别:
Genetic Analysis of Glia-to-Neuron Communication
胶质细胞与神经元通讯的遗传分析
  • 批准号:
    8461535
  • 财政年份:
    2012
  • 资助金额:
    $ 35.37万
  • 项目类别:
Regulation of Astrocyte Heterogeneity and Developmental Maturation in the CNS
中枢神经系统星形胶质细胞异质性和发育成熟的调节
  • 批准号:
    9199226
  • 财政年份:
    2012
  • 资助金额:
    $ 35.37万
  • 项目类别:
Glial Cell Regulation of Circadian Behavior
神经胶质细胞对昼夜节律行为的调节
  • 批准号:
    8035734
  • 财政年份:
    2010
  • 资助金额:
    $ 35.37万
  • 项目类别:

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