The Neural Mechanisms of Winner and Loser Effect

赢家和输家效应的神经机制

• 批准号: 10445660
• 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
• 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/10445660
• 关键词: Address; Aggressive behavior; Alpha Cell; 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; Hormonal; Human; Hypothalamic structure; Immediate-Early Genes; In Vitro; Inbred Mouse; Individual; Instinct; Investigation; Ions; Lead; Learning; Long-Term Depression; Long-Term Potentiation; Mediating; Motor; Motor Pathways; Mus; Mutagenesis; Neurosciences; Output; Pathway interactions; Patients; Pharmacology; 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; neuromechanism; novel strategies; patch clamp; relating to nervous system; response; social; stem; willingness

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 攻击性是一种在包括人类在内的物种中广泛观察到的重要社会行为。这是 被认为是一种天生的行为，因为它的表达不需要学习。凭借正确的感官 触发因素，通常与同一特定竞争对手相关，攻击性表现为一系列 刻板的运动动作。然而，表达攻击性或侵略性的准备程度各不相同 广泛地存在于个体之间。众所周知，胜利和失败的经历会对这个人做出贡献 可变性。获胜会导致攻击性增加，而失败则会降低攻击性， 这种现象称为赢家效应和输家效应。虽然获胜伴随着关键的荷尔蒙事件 和失败已经确定，获胜者和失败者效应背后的神经机制仍然存在 不太了解。我们假设一个人的攻击性是由 攻击回路的感觉运动转换效率，由以下因素决定 电路中细胞的生物物理特性和突触传递。胜利和失败的经历 改变攻击相关细胞的兴奋性和/或通讯，并最终改变 准备进攻。利用我们对雄性小鼠攻击回路的深刻理解， 在这项研究中，我们将通过三个具体目标来检验这一假设。首先，我们将同时录制 攻击性线索引起体内 13 个大脑区域的神经反应和谷氨酸能释放 沿着介导攻击性的感觉运动通路并检查反应变化 重复输赢的经历。其次，我们将使用体外膜片钳记录 研究动物攻击相关细胞的内在特性和突触传递 具有反复的获胜、失败和社交互动经历。我们的初步结果表明 攻击回路经历两阶段可塑性，首先是突触可塑性，然后是细胞可塑性， 屡屡获胜。继这一初步发现之后，在目标 3 中，我们将解决 突触可塑性对短期和长期的赢家和输家效应以及细胞可塑性的诱导。 我们研究的意义在于它解决了一个基本的神经科学问题——社会如何 经验改变大脑以影响先天行为。也将带来新的认识 关于攻击性个体差异背后的神经机制。这样的 理解最终可能会导致治疗患有以下疾病的精神病患者的新策略 夸张的攻击性。