DEVELOPMENT OF A FOS-CHANNEL RHODOPSIN TRANSGENIC MOUSE

FOS通道视紫红质转基因小鼠的研制

• 批准号: 7773255
• 负责人: ALISON L BARTH
• 金额: $ 16.66万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7773255
• 关键词: Action Potentials; Amygdaloid structure; Animals; Area; Association Learning; Back; Behavior; Behavioral; Brain; Cations; Cell membrane; Cells; Cerebral cortex; Cocaine; Communities; Complex; Coupled; Couples; Data; Development; Disease; Drug Addiction; Drug Exposure; Exons; FOS Family Genes; FOS gene; Fire - disasters; Gene Expression; Gene Fusion; Genes; Imagery; Immediate-Early Genes; In Vitro; Introns; Investigation; Ion Channel; Learning; Memory; Mental disorders; Modification; Molecular; Mus; Neurons; Neurophysiology - biologic function; Neurosciences; Nucleus Accumbens; Output; Perception; Population; Property; Proteins; Recruitment Activity; Regulation; Reporter Genes; Resources; Rhodopsin; Role; Seizures; Sensory; Sensory Process; Stimulus; Synapses; Synaptic plasticity; System; Technology; Testing; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Ventral Tegmental Area; Vibrissae; Work; addiction; conditioned fear; experience; improved; in vivo; meetings; motor learning; neural circuit; novel; overexpression; photoactivation; promoter; public health relevance; reconstitution; relating to nervous system; research study; success; synaptic function; tool; trafficking

DESCRIPTION (provided by applicant): The immediate early gene c-fos couples neural activity to gene expression and has been widely used as a marker to identify stimulus-specific neural ensembles. Here we propose to create and characterize transgenic mice that use the c-fos promoter to drive expression of the light-activated cation channel, channelrhodopsin (ChR), coupled to the yellow-fluorescent protein YFP. This proposal presents a fusion of cutting-edge technologies (direct visualization of gene expression and use of light-activated ion channels for circuit reactivation) that facilitate investigation of novel questions in systems neuroscience. Fos-ChR transgenic mice will allow us to 1) mark the identity of activated cells and 2) subsequently drive activity in these neurons to test the role of specific neurons in perception and behavior. Controlled reactivation of neuronal subsets will answer important questions about how specific neuronal subsets encode perception and behavior, and may facilitate active retraining of maladaptive neural circuits that have been altered by drug exposure or disease. PUBLIC HEALTH RELEVANCE: The mammalian brain contains millions to trillions of neurons that drive a wide array of complex behaviors. Understanding how specific neuronal ensembles are engaged by and encode perception and behavior requires identification and analysis of these neural subsets. Expression of the immediate-early gene c-fos can "mark" populations of task- or stimulus-specific neurons, providing a functional criterion to define neural subpopulations. Using fos gene promoter sequences to drive expression of the light-activated cation channel, channelrhodopsin, (ChR) we will create and characterize fos-ChR transgenic mice. These animals will enable us to identify and then reactivate functionally-defined neural ensembles to understand how the controlled reactivation of small subsets of neurons can drive perception and behavior. In addition, neural reactivation may allow retraining of specific circuits to eliminate maladaptive behaviors in addiction or psychiatric disorders.

描述（由申请人提供）：即刻早期基因c-fos将神经活性与基因表达偶联，并已被广泛用作识别刺激特异性神经系综的标记物。在这里，我们建议创建和表征转基因小鼠，使用c-fos启动子驱动表达的光激活阳离子通道，通道视紫红质（ChR），耦合到黄色荧光蛋白YFP。该提案融合了尖端技术（基因表达的直接可视化和使用光激活离子通道进行回路重新激活），促进了系统神经科学中新问题的研究。Fos-ChR转基因小鼠将允许我们1）标记激活细胞的身份，2）随后驱动这些神经元的活动，以测试特定神经元在感知和行为中的作用。神经元亚群的受控再激活将回答有关特定神经元亚群如何编码感知和行为的重要问题，并可能促进因药物暴露或疾病而改变的适应不良神经回路的主动再训练。公共卫生相关性：哺乳动物的大脑包含数百万到数万亿的神经元，这些神经元驱动着一系列复杂的行为。理解特定的神经元集合如何参与感知和行为并编码感知和行为需要识别和分析这些神经子集。即刻早期基因c-fos的表达可以“标记”任务或刺激特异性神经元的群体，提供了定义神经亚群的功能标准。使用fos基因启动子序列驱动光激活阳离子通道，通道视紫红质，（ChR）的表达，我们将创建和表征fos-ChR转基因小鼠。这些动物将使我们能够识别并重新激活功能定义的神经集合，以了解小部分神经元的受控重新激活如何驱动感知和行为。此外，神经再激活可能允许重新训练特定回路，以消除成瘾或精神疾病中的适应不良行为。