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.

项目总结/摘要 附属的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，包括 人类它在神经精神疾病或社会隔离时期（如COVID-19）的中断 大流行病可对身心健康造成严重损害。然而，神经回路机制 支配亲和性社会行为的机制还没有被很好地理解。修饰行为（修饰行为针对 另一个个体）是一种主要的附属社会接触形式，动物可以通过这种形式形成，维持， 加强社会关系，并保存在广泛的社会物种，如鸟类，蝙蝠，啮齿动物， 犬科、猫科、马科和灵长类动物。然而，神经回路背后的allorgrooming一直稀疏 但是，很少有大脑区域编码和促进亲和性的同种理毛行为。解密 亲和性同种理毛的神经回路机制将为深入了解 社会关系和依恋。考虑到几个孩子在亲密的社会行为上的明显障碍， 神经精神障碍，包括自闭症和精神分裂症，这种理解可以指导电路水平 调查疾病机制和制定干预措施。在最近的研究中，我们建立了一个 动物行为学相关和实验上易于处理的实验室研究异理行为的范例 并揭示了内侧杏仁核（MeA）至内侧视前区（MPOA）回路在控制 这种行为。这些发现为深入剖析功能电路提供了宝贵的机会 潜在的异理行为本申请的中心目标是阐明神经回路 MPOA控制异育的机制，这是朝着 定义亲和性社会行为的神经回路的功能组织。我们提出了一系列 全面探索选择MPOA神经元亚群的活性是否以及如何 而它们的下游靶点调节着异理行为。具体而言，我们将处理以下问题 重要的问题：（目的1）异理行为是由选择的，分子定义的MPOA控制的吗 亚群？(Aim 2）MPOA神经元中的神经活动动力学是否以及如何编码社会感觉 暗示和异理行为(Aim 3）MPOA下游的神经回路是什么？ 异毛行为我们提出的研究将整合最先进的技术， 操纵特定的神经元亚群，在清醒、自由 行为动物和神经投射的功能映射，以揭示特定的MPOA神经元 亚种群对同种线索作出反应，并通过下游控制异理的显示。 预测。这项研究将产生新的，关键的见解，神经回路的基础上进化 一种保守的、主要的亲和性社会行为。这些见解将影响我们对社会的理解， 凝聚力和断开，如在经历社会孤立或神经精神疾病的个人。