Neural Circuit Mechanisms of Allogrooming Behavior

项目摘要/摘要 附属社会相互作用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。在神经精神疾病中或在社会孤立时期，如新冠肺炎 大流行会严重损害人们的身心健康。然而，神经回路机制 对附属社会行为的管理还没有得到很好的理解。异型美容(针对 另一个人)是一种主要的附属社会联系形式，动物可以通过这种联系形成、维持和 加强社会关系，在广泛的社会物种中受到保护，如鸟类、蝙蝠、啮齿动物、 犬科动物、猫科动物、马科动物和灵长类动物。然而，异体美容背后的神经回路一直很稀少。 研究发现，编码和促进从属异体修饰的大脑区域很少。破译 附属异物修剪的神经回路机制将提供对潜在的神经基础的关键见解 社会联系和依恋。考虑到在几个方面的附属社会行为方面的显著障碍 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层面 疾病机制的调查和干预措施的发展。在最近的研究中，我们建立了一个 在实验室研究异体整容行为的行为学相关和实验上易处理的范式 并发现杏仁内侧核(Mea)到视前内侧区(MPOA)的环路在控制 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 潜在的异种美容行为。这项应用的中心目标是阐明神经回路 MPOA控制异地整理的机制，这是实现以下目标的关键下一步 定义附属社会行为的神经回路的功能组织。我们提出了一系列 综合探讨精选MPOA神经元亚群是否及如何活动的实验 而它们的下游目标则监管着异种美容行为。具体地说，我们将解决以下问题 重要问题：(目标1)异体美容行为是由选择的、分子定义的MPOA控制的 亚群？(目标2)MPOA神经元的神经活动动力学是否以及如何编码社会感觉 暗示和异形打扮行为？(目标3)MPOA下游有哪些神经回路负责调节 异形打扮的行为？我们提议的研究将结合最先进的技术来实现函数 特定神经元亚群的操纵，清醒时神经元活动动力学的活体成像，自由 动物行为，以及神经投射的功能图谱，以揭示特定的MPOA神经元 亚群对同种线索做出反应，并通过其下游控制异种毛发的显示 投射。这项研究将对进化过程中潜在的神经回路产生新的、批判性的见解 保守的，附属的社会行为的主要形式。这样的见解将影响我们对社会的理解 凝聚力和脱节，例如在经历社会孤立或神经精神障碍的个人中。

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.