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Function of RGS2 in Serotonin Neurons and Anxiety

RGS2 在血清素神经元和焦虑中的功能

基本信息

批准号：
8235746
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
项目类别：
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/8235746
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

项目摘要

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 (RGS) 通过加速或阻断 G 蛋白效应来确定细胞内 G 蛋白信号的反应。 RGS 蛋白家族的成员之一 RGS2 最近被描述为与小鼠的攻击性和焦虑行为有关。行为表型将 RGS2 的作用与大脑中的血清素递质系统联系起来，该系统参与控制攻击性和焦虑。我们将通过使用 RGS2(-/-) 小鼠与小鼠组合来研究 RGS2 在生理学和血清素能系统发育中的作用，其中血清素能递质系统在血清素能特异性启动子下表达 YFP。这些小鼠将用于识别发育过程中的血清素能神经元和进行电生理记录，并使我们能够比较基因敲除动物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内增加和/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，了解当动物的行为状态因 RGS2 的缺失或存在而改变时，血清素能系统的神经元回路的生理和发育如何改变。公共健康相关性：这项研究的重要性在于，我们对 RGS 蛋白调节血清素信号传导的功能一无所知，而且关于血清素系统如何自我调节的信息也很少。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，而且对受血清素影响和调节的其他行为和生理反应也有重大影响，例如攻击性、昼夜节律、血压和呼吸。