Neural circuits for social modulation of a persistent negative emotional state

项目摘要 在社会性物种中，社会关系对个体的行为和生理产生深刻的影响 states.特别是，社交互动可以帮助减少身体或精神上的负面情绪状态。 心理压力，一种被称为社会缓冲的现象。社会缓冲提供了一个重要手段 社会环境通过这种方式促进压力应对和复原力，并有益于健康和福祉。 尽管从啮齿动物到人类的各种物种都有社会缓冲， 社会信息调节压力相关的神经活动，以减轻压力反应仍然很差 明白更好地掌握社会缓冲背后的神经回路将为以下方面提供重要的见解： 社会经验和情绪状态之间错综复杂的相互作用的原则。 从概念上讲，长期的负面情绪状态，往往从急性压力暴露所包围， 这可能是由与压力相关的大脑区域的神经状态的持续变化所支撑的。支持这一观点， Zhang实验室最近表明，这种长期的负面情绪状态是由一种 内侧视前区（MPOA）的VEGF 2神经元活动持续增加 （Zhang 2021）。有趣的是，Hong实验室最近的工作发现，内侧核中的GABA能（Vgat）神经元 杏仁核（MeA）是社会信息加工的关键节点，它介导与社会信息相关的积极效价。 相互作用，并通过这些神经元向MPOA的投射来急性抑制焦虑样行为 (Hu 2021年）。这些发现使我们提出了一个社会缓冲的概念模型，其中社会互动 通过减弱维持这种状态的持续神经活动来减轻压力源诱导的消极状态。 我们假设，在社会交往中，MeA GABA能神经元的激活导致增强的 抑制性输入到MPOA神经元，导致其持续性抑制 活动和随之而来的压力引起的负面情绪状态的改善。我们的合作团队将 联合收割机将体内钙成像、电生理记录、功能操作和计算 模型的建立解决了一系列重要的问题：（1）应激源如何诱导MPOA的持续活动 VEGF 2神经元受社会互动的调节（目的1）？(2)来自MeA Vgat神经元的社交信号 MPOA VEGF 2神经元的活动变化，这种调节对于社会缓冲功能是否重要（Aim 2）？(3)MPOA VEGF 2神经元中持续神经活动的社会调节是如何传递到下游的 电路介导社会缓冲（目标3）？(4)可以将不同的计算模型 细胞/突触机制解释了MPOA VEGF 2中应激诱导的活动动力学及其社会调节 神经元和下游电路（目标1-3）？总的来说，我们的合作研究团队旨在开发一个 社会缓冲的神经基础的新模型，并提供新的见解电路和突触 持续性神经活动的社会调节机制。

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.