Function of RGS2 in Serotonin Neurons and Anxiety

RGS2 在血清素神经元和焦虑中的功能

• 批准号: 7803736
• 负责人: STEFAN HERLITZE
• 金额: $ 24.17万
• 依托单位: RUHR-UNIVERSITAT BOCHUM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7803736
• 关键词: Aggressive behavior; Amygdaloid structure; Animals; Anxiety; Automobile Driving; Behavior; Behavioral; Blood Pressure; Brain; Breathing; Circadian Rhythms; Cognition; Computer Systems Development; Data; Development; Diffuse; Dominant-Negative Mutation; Electrophysiology (science); Emotions; Enhancers; Event; Family member; Fluorescence; G-Protein-Coupled Receptors; GTP-Binding Protein Regulators; GTP-Binding Proteins; Goals; Grant; Hippocampus (Brain); Hypertension; Hypothalamic structure; Investigation; Knock-out; Knockout Mice; Knowledge; Laboratories; Link; Longevity; Memory; Moods; Mus; Nervous system structure; Neurons; Output; Pathway interactions; Phenotype; Physiological; Physiology; Play; Prefrontal Cortex; Principal Investigator; Property; Protein Family; Proteins; Quantitative Trait Loci; RGS Proteins; RGS2 gene; Receptor Mediated Signal Transduction; Receptor Signaling; Regulation; Role; Serotonin; Sex Behavior; Signal Pathway; Signal Transduction; Sleep Wake Cycle; Slice; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; System; Testing; Transgenic Animals; Transgenic Mice; Wild Type Mouse; base; behavior change; design; extracellular; insight; member; mutant; postsynaptic; presynaptic; programs; promoter; public health relevance; receptor; response; transcription factor

DESCRIPTION (provided by applicant): G proteins convert extracellular signals to intracellular events. Regulator of G protein signaling proteins (RGS) determine the response of the intracellular G protein signals by accelerating or blocking the G protein effects. One member of the RGS protein family, RGS2, has recently been described to be associated with aggressive and anxious behaviors in mice. The behavioral phenotypes link the RGS2 action to the serotonergic transmitter system in brain, which is involved in control of aggression and anxiety. We will investigate here the role of RGS2 for the physiology and the development of the serotonergic system by using RGS2(-/-) mice in combination with mice, where the serotonergic transmitter system expresses YFP under a serotonergic specific promotor. These mice will be used to identify serotonergic neurons during development and for electrophysiological recordings and will allow us to compare the neuronal networks between knock-out and wild-type animals. In addition we will create transgenic animals where RGS2 function is increased and/or decreased within the serotonergic system, to demonstrate that RGS2 has specific functions for regulating neuronal circuits involved in anxiety. Thus, the overall goal of this grant is to gain new insight into how neuronal circuits of the serotonergic system are altered in their physiology and development when the behavioral state of the animal is altered by the absence or presence of RGS2. PUBLIC HEALTH RELEVANCE: The importance of this study lies in the fact that nothing is known about the function of RGS proteins for regulating serotonergic signaling and that very little information is available on how the serotonergic system regulates itself. The study may therefore have major impact on our understanding of the regulation of anxiety states, but also other behaviors and physiological responses influenced and modulated by serotonin, such as aggression, circadian rhythm, blood pressure and breathing.

描述（由申请人提供）：G蛋白将细胞外信号转化为细胞内事件。G蛋白信号调节蛋白（Regulator of G protein signaling proteins，RGS）通过加速或阻断G蛋白的作用，决定细胞内G蛋白信号的应答。RGS蛋白家族的一个成员RGS 2最近被描述为与小鼠的攻击性和焦虑行为相关。行为表型将RGS 2的作用与大脑中的多巴胺能递质系统联系起来，该系统参与控制攻击和焦虑。我们将在这里研究RGS 2的生理作用和发展的多巴胺能系统通过使用RGS 2（-/-）小鼠与小鼠组合，其中多巴胺能递质系统表达YFP下的多巴胺能特异性启动子。这些小鼠将用于在发育过程中识别多巴胺能神经元和进行电生理记录，并使我们能够比较基因敲除和野生型动物之间的神经元网络。此外，我们将创建转基因动物，其中RGS 2的功能增加和/或减少的多巴胺能系统，以证明RGS 2具有调节参与焦虑的神经元回路的特定功能。因此，这项资助的总体目标是获得新的见解，了解当动物的行为状态因RGS 2的存在或不存在而改变时，多巴胺能系统的神经元回路在其生理和发育中如何改变。公共卫生关系：这项研究的重要性在于，我们对RGS蛋白调节β-肾上腺素能信号传导的功能一无所知，而且关于β-肾上腺素能系统如何调节自身的信息也很少。因此，这项研究可能会对我们理解焦虑状态的调节产生重大影响，但也会影响和调节血清素影响的其他行为和生理反应，如攻击性，昼夜节律，血压和呼吸。