The Neural Mechanisms of Winner and Loser Effect

摘要 攻击性是一种重要的社会行为，在包括人类在内的物种中广泛观察到。是 它被认为是一种天生的行为，因为它的表达不需要学习。有了正确的感官 触发器，通常与同种竞争者有关，侵略性被表达为一系列 刻板的运动动作然而，表达侵略性，或侵略性的准备程度各不相同 广泛存在于个体之间。输赢的经历对这个人的影响是众所周知的 可变性赢了会增加攻击性，输了会减少攻击性， 这就是所谓的赢家和输家效应。虽然关键的荷尔蒙事件伴随着胜利 虽然已经确定了输赢，但赢家和输家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 侵略电路的感觉-运动转换的效率，这是由 生物物理性质和突触传递的细胞在电路中。输赢经验 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， 本研究将通过三个具体目标来检验这一假设。首先，我们将同时记录 攻击性线索诱发了在体神经反应和13个脑区神经递质释放 沿着调节攻击性的感觉-运动通路， 反复的赢和输的经历。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 有着反复的输赢和社会互动的经历。我们的初步结果显示， 攻击回路经历两个阶段的可塑性，首先是突触可塑性，然后是细胞可塑性， 多次获胜。根据这一初步发现，在目标3中，我们将讨论 突触可塑性的短期和长期赢家和输家效应和诱导细胞可塑性。 我们研究的重要性在于它解决了一个基本的神经科学问题--社会性如何 经验会改变大脑，从而影响先天行为。它也将提供新的理解 关于个体攻击性差异背后的神经机制。等 理解可能最终导致新的战略，治疗精神病患者患有 夸张的侵略。

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.