Neural circuits for social modulation of a persistent negative emotional state

持续负面情绪状态的社会调节的神经回路

• 批准号: 10721276
• 负责人: Weizhe Hong
• 金额: $ 324.1万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10721276
• 关键词: Acute; Address; Amygdaloid structure; Anxiety; Area; Attenuated; Behavior; Behavioral; Brain; Buffers; COVID-19 pandemic; Computer Analysis; Computer Models; Development; Electrophysiology (science); Emotional; Endoscopy; Glutamates; Health Benefit; Hour; Human; Individual; Laboratory Finding; Life; Loneliness; Major Depressive Disorder; Medial; Mediating; Mental Depression; Mental Health; Modeling; Mus; Neurons; Pathway interactions; Personal Satisfaction; Physiological; Population Dynamics; Positive Valence; Post-Traumatic Stress Disorders; Preoptic Areas; Psyche structure; Public Health; Research; Risk; Rodent; Role; Series; Signal Transduction; Social Environment; Social Interaction; Social Well-Being; Social isolation; Stress; Stress and Coping; Synapses; Synaptic plasticity; System; Work; acute stress; anxiety-like behavior; biological adaptation to stress; effective intervention; experience; grasp; high dimensionality; in vivo calcium imaging; information processing; insight; midbrain central gray substance; negative emotional state; neural; neural circuit; neural model; novel; optogenetics; positive emotional state; psychological stressor; social; social neuroscience; social relationships; stress resilience; stressor; theories

PROJECT SUMMARY In social species, social relationships can exert profound influences on individuals’ behavioral and physiological states. In particular, social interactions can help reduce negative emotional state induced by physical or psychological stressors, a phenomenon known as social buffering. Social buffering provides an important means by which the social environment facilitates stress coping and resilience and benefits health and well-being. Despite the conservation of social buffering in a wide range of species from rodents to humans, how incoming social information modulates stress-related neural activity to mitigate stress responses remains poorly understood. A better grasp of the neural circuitry underlying social buffering will provide critical insights into principles governing the intricate interaction between social experience and emotional state. Conceptually, the long-lasting negative emotional state that often ensues from acute stress exposure is likely underpinned by persistent changes in neural states in stress-related brain areas. Supporting this notion, the Zhang lab recently showed that this long-lasting negative emotional state is represented and controlled by a persistent increase of neural activity in glutamatergic (Vglut2) neurons in the medial preoptic area (MPOA) (Zhang 2021). Interestingly, recent work from the Hong lab found that GABAergic (Vgat) neurons in the medial amygdala (MeA), a key node in social information processing, mediates positive valence associated with social interactions and acutely suppresses anxiety-like behavior through the projections of these neurons to the MPOA (Hu 2021). These findings led us to propose a conceptual model for social buffering in which social interactions mitigate stressor-induced negative state by attenuating persistent neural activity that maintains this state. We hypothesize that activation of MeA GABAergic neurons during social interactions leads to enhanced inhibitory input into MPOA glutamatergic neurons, resulting in a long-lasting suppression of their persistent activity and a consequent amelioration of stressor-induced negative emotional state. Our collaborative team will combine in vivo calcium imaging, electrophysiological recording, functional manipulation, and computational modeling to address a series of important questions: (1) How is stressor-induced persistent activity in MPOA Vglut2 neurons modulated by social interaction (Aim 1)? (2) Do social signals from MeA Vgat neurons drive activity changes in MPOA Vglut2 neurons and is this modulation functionally important for social buffering (Aim 2)? (3) How is social modulation of persistent neural activity in MPOA Vglut2 neurons relayed to downstream circuits to mediate social buffering (Aim 3)? (4) Can computational models that incorporate different cellular/synaptic mechanisms explain stress-induced activity dynamics and its social modulation in MPOA Vglut2 neurons and downstream circuits (Aims 1–3)? Collectively, our collaborative research team aims to develop a novel model for the neural basis of social buffering and to provide new insights into the circuit and synaptic mechanisms underlying the social modulation of persistent neural activity.

项目摘要 在社会物种中，社会关系可以对个人的行为和生理影响产生深远的影响 国家。特别是，社交互动可以帮助减少由身体或 心理压力源，一种被称为社会缓冲的现象。社会缓冲提供了重要的手段 社会环境促进了压力应对和韧性，并使健康与福祉受益。 尽管从啮齿动物到人类的广泛物种中保存了社交缓冲 社会信息调节与压力相关的神经活动以减轻压力反应仍然很差 理解。更好地了解社会缓冲的神经电路将提供关键的见解 负责社会经验与情绪状态之间复杂互动的原则。 从概念上讲，急性压力暴露经常出现的持久的负面情绪状态是 与压力相关的大脑区域中神经状态的持续变化可能是基础的。支持这个概念， 张实验室最近表明，这种持久的负面情绪状态由 谷氨酸能（VGLUT2）神经元（MPOA）中神经元活性的持续增加 （张2021）。有趣的是，洪实验室的最近工作发现媒体中的GABA能（VGAT）神经元 社会信息处理中的关键节点Amygdala（MEA）调解与社会相关的积极价 通过这些神经元对MPOA的投影，相互作用并急性抑制动画样的行为 （Hu 2021）。这些发现使我们提出了一个社会互动的社会缓冲的概念模型 通过衰减维持该状态的持续性神经活动来减轻压力诱导的负状态。 我们假设社交互动过程中MEA GABA能神经元的激活导致增强 对MPOA谷氨酸能神经元的抑制作用，导致对其持续的持续抑制 活动和随之而来的压力诱导的负面情绪状态的改善。我们的协作团队将 结合体内钙成像，电生理记录，功能操纵和计算 建模以解决一系列重要的问题：（1）压力诱导的MPOA持续活动如何 通过社会互动调节的VGLUT2神经元（AIM 1）？ （2）从MEA VGAT神经元驱动器进行社交信号 MPOA VGLUT2神经元的活动变化，并且该调制在社交缓冲功能上很重要（AIM 2）？ （3）MPOA VGLUT2神经元中持续性神经元活动的社会调节如何传递到下游 电路调节社会缓冲（AIM 3）？ （4）可以包含不同的计算模型 细胞/突触机制解释了压力诱导的活性动力学及其在MPOA VGLUT2中的社会调制 神经元和下游电路（目标1-3）？总的来说，我们的协作研究团队旨在开发 社会缓冲神经元基础的新型模型，并为电路提供新的见解和突触 持续神经活动的社会调节的基础机制。