Neural Circuit Mechanisms of Allogrooming Behavior

梳理行为的神经回路机制

• 批准号: 10512359
• 负责人: Weizhe Hong
• 金额: $ 68.78万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-17 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10512359
• 关键词: Address; Adult; Affective; Amygdaloid structure; Animals; Area; Axon; Behavior; Behavioral; Birds; Brain; COVID-19 pandemic; Calcium; Cells; Chiroptera; Complex; Cues; Data; Development; Disease; Dissection; Distress; Felis catus; Female; Gene Expression; Grooming; Heterogeneity; Human; Image; Imaging Techniques; Impairment; Individual; Investigation; Laboratory mice; Life; Mammals; Medial; Mediating; Mental disorders; Molecular; Mus; Neurons; Neuropeptides; Oxytocin; Pattern; Personal Satisfaction; Physiological; Play; Population; Preoptic Areas; Primates; Psyche structure; Public Health; Regulation; Reproduction; Research; Resolution; Rodent; Role; Schizophrenia; Sensory; Series; Social Behavior; Social Interaction; Social Well-Being; Social isolation; Stress; Structure; Subgroup; Symptoms; Techniques; Testing; Time; Touch sensation; Ventral Tegmental Area; affiliative behavior; autism spectrum disorder; awake; base; cell type; effective therapy; endogenous opioids; experience; experimental study; gene function; in vivo; in vivo imaging; insight; male; midbrain central gray substance; neural circuit; neuropsychiatric disorder; neuropsychiatry; novel; optogenetics; psychopathic personality; relating to nervous system; social; social attachment; social cohesion; social contact; social relationships; therapy development; transcriptomics

Project Summary/Abstract Affiliative social interactions play an essential role in the reproduction and survival of social species including humans. Its disruption in neuropsychiatric conditions or during times of social isolation such as the COVID-19 pandemic can take a heavy toll on mental and physical well-being. However, the neural circuit mechanisms governing affiliative social behaviors are not well understood. Allogrooming (grooming behavior directed toward another individual) is a major form of affiliative social contact through which animals may form, maintain, and strengthen social relationships and is conserved in a wide range of social species, such as birds, bats, rodents, canids, cats, equids, and primates. However, the neural circuitry underlying allogrooming has been sparsely explored and few brain areas that encode and promote affiliative allogrooming have been identified. Deciphering the neural circuit mechanisms of affiliative allogrooming will provide key insights into the neural basis underlying social affiliation and attachment. Given the prominent impairment in affiliative social behavior in several neuropsychiatric disorders, including autism and schizophrenia, this understanding can guide circuit-level investigation of disease mechanisms and development of interventions. In recent studies, we established an ethologically relevant and experimentally tractable paradigm for studying allogrooming behavior in laboratory mice and uncovered a key role of a medial amygdala (MeA)-to-medial preoptic area (MPOA) circuit in controlling this behavior. These findings open up valuable opportunities for in-depth dissection of the functional circuitry underlying allogrooming behavior. The central objective of this application is to elucidate the neural circuit mechanisms through which the MPOA controls allogrooming, which represents a critical next step toward defining the functional organization of the neural circuitry of affiliative social behavior. We propose a series of experiments to comprehensively probe whether and how the activity of select MPOA neuronal subpopulations and their downstream targets regulate allogrooming behavior. Specifically, we will address the following important questions: (Aim 1) Is allogrooming behavior controlled by select, molecularly defined MPOA subpopulations? (Aim 2) Whether and how neural activity dynamics in MPOA neurons encodes social sensory cues and allogrooming behavior? (Aim 3) What are the neural circuits downstream of the MPOA that mediate allogrooming behavior? Our proposed research will integrate state-of-the-art techniques for functional manipulation of specific neuronal subpopulations, in vivo imaging of neuronal activity dynamics in awake, freely behaving animals, and functional mapping of neural projections to reveal how specific MPOA neuronal subpopulations respond to conspecific cues and control the display of allogrooming through their downstream projections. This investigation will yield novel, critical insights into the neural circuitry underlying an evolutionarily conserved, major form of affiliative social behavior. Such insights will impact our understanding of social cohesion and disconnection, such as in individuals experiencing social isolation or neuropsychiatric disorders.

项目摘要/摘要 从属社会互动在社会物种的繁殖和生存中起着至关重要的作用 人类。它在神经精神病条件下或在社会隔离时期（例如Covid-19）的破坏 大流行会对精神和身体健康造成巨大损失。但是，神经回路机制 理事的社会行为尚未得到充分理解。分配室（修饰行为针对 另一个人）是一种主要形式的从属社会接触，动物可以形成，维护和 加强社会关系，并在各种社会物种中保存，例如鸟类，蝙蝠，啮齿动物， 犬科，猫，钟表和灵长类动物。但是，依据的神经电路很少 已经确定了经过探索和促进隶属关系的大脑区域。解密 隶属分配室的神经回路机制将为基础神经基础提供关键的见解 社会隶属和依恋。鉴于几个属属社会行为的显着损害 神经精神疾病，包括自闭症和精神分裂症，这种理解可以指导电路级别 研究疾病机制和干预措施的发展。在最近的研究中，我们建立了 在伦理上相关且具有实验性的范式，用于研究实验室的分配行为 小鼠并发现了内侧杏仁核（MEA）对中部前区域（MPOA）电路的关键作用 这种行为。这些发现为功能电路的深入解剖开辟了宝贵的机会 基本的分配行为。该应用的核心目的是阐明神经回路 MPOA控制同层的机制，这代表了迈向下一步的关键步骤 定义隶属社会行为神经循环的功能组织。我们提出了一系列 实验以全面探测选择MPOA神经元亚群的活性以及如何 他们的下游目标调节了同种异体行为。具体来说，我们将解决以下内容 重要问题：（ AIM 1）是由选择，分子定义的MPOA控制的分配行为 亚群？ （目标2）MPOA神经元中的神经活动动态是否以及如何编码社会感觉 提示和分配行为？ （AIM 3）MPOA下游的神经电路是什么介导的 异种行为？我们拟议的研究将整合最新的功能技术 操纵特定的神经元亚群，在醒着中神经元活性动力学的体内成像，自由 行为动物以及神经投影的功能映射，以揭示特定MPOA神经元如何 亚群对特定的提示做出响应，并通过其下游控制同层的展示 预测。这项研究将产生对进化的神经回路的新颖，关键的见解 保守的，主要的从属社会行为。这样的见解将影响我们对社会的理解 凝聚力和断开连接，例如在经历社会隔离或神经精神疾病的个人中。