The Neural Mechanisms of Winner and Loser Effect

赢家和输家效应的神经机制

基本信息

批准号：
10705810
负责人：
Dayu Lin
金额：
$ 61.32万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-16 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705810
关键词：
Address Aggressive behavior Amygdaloid structure Animals Automobile Driving Behavior Biophysics Brain Brain region Cells Chemosensitization Communication Cues Data Development Estrogen Receptor alpha Event Fiber Future Generations Genetic Glutamates Goals Gonadal Steroid Hormones Homosynaptic Depression Hormonal Human Hypothalamic structure Immediate-Early Genes In Vitro Inbred Mouse Individual Instinct Investigation Ions Learning Long-Term Depression Long-Term Potentiation Mediating Motor Motor Pathways Mus Mutagenesis Neurosciences Output Pathway interactions Patients Phase Population Property Protocols documentation Readiness Research Resources Risk Role Secure Sensory Series Site Slice Social Behavior Social Interaction Societies Stereotyping Synapses Synaptic Transmission Synaptic plasticity Testing Variant Violence biophysical properties experience experimental study fighting in vivo in vivo monitoring individual variation insight male neural neuromechanism novel strategies patch clamp pharmacologic response social stem willingness

Address Aggressive behavior Amygdaloid structure Animals Automobile Driving Behavior Biophysics Brain Brain region Cells Chemosensitization Communication Cues Data Development Estrogen Receptor alpha Event Fiber Future Generations Genetic Glutamates Goals Gonadal Steroid Hormones Homosynaptic Depression Hormonal Human Hypothalamic structure Immediate-Early Genes In Vitro Inbred Mouse Individual Instinct Investigation Ions Learning Long-Term Depression Long-Term Potentiation Mediating Motor Motor Pathways Mus Mutagenesis Neurosciences Output Pathway interactions Patients Phase Population Property Protocols documentation Readiness Research Resources Risk Role Secure Sensory Series Site Slice Social Behavior Social Interaction Societies Stereotyping Synapses Synaptic Transmission Synaptic plasticity Testing Variant Violence biophysical properties experience experimental study fighting in vivo in vivo monitoring individual variation insight male neural neuromechanism novel strategies patch clamp pharmacologic response social stem willingness

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项目摘要

ABSTRACT Aggression is an important social behavior widely observed across species, including humans. It is considered an innate behavior because its expression requires no learning. With the right sensory trigger, often one associated with conspecific competitors, aggression is expressed as a series of stereotyped motor actions. However, the readiness to express aggression, or aggressiveness, varies widely among individuals. Experiences of winning and losing are known to contribute to this individual variability. Winning leads to an increase in aggressiveness while losing decreases aggressiveness, a phenomenon termed the winner and loser effect. While key hormonal events accompanying winning and losing have been identified, the neural mechanisms underlying the winner and loser effect remain poorly understood. We hypothesize that the aggressiveness of an individual is determined by the efficiency of sensory-motor transformation of the aggression circuit, which is determined by the biophysical properties and synaptic transmission of cells in the circuit. Winning and losing experiences alter the excitability and/or communication of aggression-related cells and ultimately changes the readiness to attack. Leveraging upon our deep understanding of the aggression circuit in male mice, in this study we will test this hypothesis through three specific aims. First, we will simultaneously record the aggression-cue evoked in vivo neural responses and glutamatergic release from 13 brain regions along the sensory-motor pathway that mediates aggression and examine the response changes over repeated winning and losing experiences. Second, we will use in vitro patch clamp recording to investigate the intrinsic properties and synaptic transmission of aggression-related cells from animals with repeated winning, losing and social interaction experiences. Our preliminary results revealed that the aggression circuit undergoes two-stage plasticity, first synaptic plasticity and then cellular plasticity, over repeated winning. Following up on this initial finding, in Aim 3, we will address the contribution of synaptic plasticity to short- and long-term winner and loser effect and the induction of cellular plasticity. The significance of our study is that it addresses a fundamental neuroscience question -- how social experience alters the brain to influence innate behaviors. It will also provide new understanding regarding the neural mechanisms underlying individual variability in aggressiveness. Such understanding could ultimately lead to novel strategies for treating psychiatric patients suffering from exaggerated aggression.

抽象的侵略是包括人类在内的物种中广泛观察到的重要社会行为。这是被认为是天生的行为，因为它的表达不需要学习。与正确的感觉触发器，通常是与同种竞争者有关的触发因素，侵略性表示为一系列定型的运动动作。但是，表达侵略或侵略性的准备就会有所不同在个人中广泛。众所周知，获胜和失败的经历会为这个人做出贡献可变性。胜利导致侵略性提高，而输掉的侵略性降低了侵略性，现象称为获胜者和失败者效应。伴随获胜的关键荷尔蒙事件并且已经确定了失败，获胜者和失败者效应的基础神经机制仍然存在理解不佳。我们假设一个人的侵略性由侵略回路的感觉运动转化的效率，这取决于电路中细胞的生物物理特性和突触传播。获胜和失去经验改变与攻击相关细胞的兴奋性和/或通信，并最终改变准备进攻。利用我们对雄性小鼠侵略回路的深入了解，这项研究将通过三个特定目标检验这一假设。首先，我们将同时记录侵略性提示引起了体内神经反应和谷氨酸能释放的13个大脑区域沿着介导侵略性并检查反应变化的感觉运动途径反复的获胜和失去经历。其次，我们将使用体外贴片夹记录到研究来自动物的侵略性细胞的内在特性和突触传播一再赢得胜利，失败和社交互动经验。我们的初步结果表明侵略性电路经历了两阶段的可塑性，首先是突触可塑性，然后是细胞塑性，然后反复胜利。跟进这一初步发现，在AIM 3中，我们将解决突触可塑性对短期和长期赢家和失败者效应以及诱导细胞可塑性。我们研究的意义在于它解决了一个基本的神经科学问题 - 如何社会经验会改变大脑以影响先天的行为。它还将提供新的理解关于侵略性的个体变异性的神经机制。这样的理解最终可能会导致治疗患有精神病患者的新型策略夸张的侵略。