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（由申请人提供）：G蛋白将细胞外信号转换为细胞内事件。 G蛋白信号蛋白（RGS）的调节剂通过加速或阻断G蛋白效应来确定细胞内G蛋白信号的响应。 RGS蛋白质家族RGS2的一位成员最近被描述为与小鼠的侵略性和焦虑行为有关。行为表型将RGS2作用与大脑中的血清素能发射器系统联系起来，该系统与控制攻击和焦虑有关。我们将在这里研究RGS2通过使用RGS2（ - / - ）小鼠与小鼠结合使用RGS2（ - / - ）小鼠的生理和发展的作用，在这些小鼠中，血清素能发射机系统在5-羟色胺能特异性促销中表达YFP。这些小鼠将用于在发育过程中和电生理记录过程中鉴定血清素能神经元，并使我们能够比较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RGS2功能在血清素能系统中增加和/或降低，以证明RGS2具有调节涉及焦虑涉及的神经元回路的特定功能。因此，这项赠款的总体目标是获得新的见解，即当动物的行为状态因不存在RGS2而改变或存在时，血清素能系统的神经元电路如何改变其生理和发育。公共卫生相关性：这项研究的重要性在于事实，即RGS蛋白在调节血清素能信号方面的功能一无所知，关于血清素能系统如何调节其本身的信息很少。因此，这项研究可能对我们对焦虑状态调节的理解产生重大影响，以及其他行为和生理反应受到5-羟色胺的影响和调节，例如侵略性，昼夜节律，血压和呼吸。