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: 8109412
• 负责人: STEFAN HERLITZE
• 金额: $ 23.93万
• 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/8109412
• 关键词: Aggressive behavior; Amygdaloid structure; Animals; Anxiety; Automobile Driving; Behavior; Behavioral; Blood Pressure; Brain; Breathing; Circadian Rhythms; Cognition; 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; Systems Development; 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(申请人提供)：G蛋白将细胞外信号转换为细胞内事件。G蛋白信号蛋白调节因子(RGS)通过加速或阻断G蛋白的作用来决定细胞内G蛋白信号的反应。RGS蛋白家族的一个成员，RGS2，最近被描述与小鼠的攻击和焦虑行为有关。行为表型将RGS2的活动与大脑中参与控制攻击和焦虑的5-羟色胺能递质系统联系起来。在这里，我们将通过使用RGS2(-/-)小鼠和小鼠来研究RGS2在生理和5-羟色胺能系统发育中的作用，其中5-羟色胺能递质系统在5-羟色胺能特异性启动子下表达YFP。这些小鼠将被用来识别发育过程中的5-羟色胺能神经元，并用于电生理记录，并将使我们能够比较基因敲除动物和野生动物之间的神经元网络。此外，我们将创建转基因动物，其中RGS2功能在5-羟色胺能系统中增加和/或减少，以证明RGS2具有调节与焦虑有关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，当动物的行为状态因RGS2的存在或缺失而改变时，5-羟色胺能系统的神经元回路在其生理和发育过程中是如何改变的。公共卫生相关性：这项研究的重要性在于，人们对RGS蛋白调节5-羟色胺能信号的功能一无所知，而且关于5-羟色胺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，但也会对5-羟色胺影响和调节的其他行为和生理反应产生重大影响，如攻击性、昼夜节律、血压和呼吸。