The Neural Mechanisms of Winner and Loser Effect

赢家和输家效应的神经机制

• 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
• 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

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.

摘要 攻击性是一种重要的社会行为，在包括人类在内的各种物种中被广泛观察到。它是 被认为是与生俱来的行为，因为它的表达不需要学习。有正确的感官 触发点，通常与同种竞争对手有关，攻击性表现为一系列 刻板印象的运动动作。然而，表达攻击性或攻击性的准备程度各不相同 在个人中广泛存在。众所周知，成功和失败的经历对这个人有贡献。 可变性。赢了会增加攻击性，而输了会降低攻击性。 这种现象被称为赢家效应和输家效应。同时伴随着获胜的关键荷尔蒙事件 已经确定了输家和赢家，但赢家和输家效应背后的神经机制仍然存在 人们对此知之甚少。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 回路中细胞的生物物理特性和突触传递。得失经验 改变攻击相关细胞的兴奋性和/或通讯，最终改变 准备好进攻了。利用我们对雄性小鼠攻击回路的深刻理解，在 在这项研究中，我们将通过三个具体的目标来检验这一假设。首先，我们将同步录制 攻击线索在体内诱发的神经反应和13个脑区的谷氨酸能释放 沿着调节攻击的感觉-运动通路，检查反应的变化 反复的输赢经历。第二，我们将使用体外膜片钳记录来 研究动物攻击相关细胞的内在特性和突触传递 有反复的输赢和社交经验。我们的初步结果显示， 攻击回路经历了两个阶段的可塑性，首先是突触可塑性，然后是细胞可塑性， 一次次的胜利。根据这一初步调查结果，在目标3中，我们将讨论 突触可塑性对短期和长期赢家和输家的影响以及对细胞可塑性的诱导。 我们这项研究的意义在于，它解决了一个基本的神经科学问题--社会性 经验会改变大脑，从而影响天生的行为。它还将提供新的理解 关于攻击性个体差异背后的神经机制。是这样的 了解这一点可能最终导致治疗患有精神疾病的精神病人的新策略 夸张的攻击性。