Neuroendocrine circuits for engagement in affiliative social interactions

参与附属社交互动的神经内分泌回路

• 批准号: 10516953
• 负责人: Ioana Carcea
• 金额: $ 47.95万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516953
• 关键词: Address; Adult; Amygdaloid structure; Animals; Automobile Driving; Behavior; Behavior Therapy; Behavioral; Behavioral Paradigm; Biological; Biology; Brain; COVID-19 pandemic; Cells; Cessation of life; Child; Chronic Disease; Clinical Trials; Cues; Data; Electrophysiology (science); Feeling; Feeling suicidal; Female; Future; General Population; Goals; Grant; Habitats; Health; Hormones; Housing; Human; Hypothalamic structure; Impairment; Incentives; Investigation; Life Style; Loneliness; Longevity; Mediating; Mental Depression; Mental Health; Modeling; Monitor; Mus; Neurons; Neuropeptides; Neurosecretory Systems; Optics; Output; Oxytocin; Oxytocin Receptor; Pattern; Peripheral; Persons; Pharmaceutical Preparations; Play; Population; Primates; Psychological reinforcement; Research; Rewards; Risk; Role; Signal Transduction; Social Behavior; Social Conditions; Social Interaction; Social Reinforcement; Social isolation; Social outcome; Stimulus; Stress; Structure; Testing; Therapeutic; Therapeutic Intervention; Time; Ventral Tegmental Area; Video Recording; Work; affiliative behavior; autism spectrum disorder; base; computerized tools; design; disorder risk; environmental change; experimental study; global health; individuals with autism spectrum disorder; innovation; mature animal; neural circuit; novel; optogenetics; pandemic disease; paraventricular nucleus; premature; prevent; pup; receptor; relating to nervous system; response; social; social engagement; social structure; stress management; therapeutic target; tool

Engaging in affiliative social interactions predicts health and longevity. The hormone oxytocin, which is released by specialized neurons in the hypothalamus, has been shown to play an important role in affiliative behaviors. However, the mechanisms that control activity of oxytocin neurons and by which these neurons might then control engagement in social interactions, have not yet been elucidated. Our long-term goal is to dissect the neuroendocrine mechanisms driving voluntary engagement in affiliative social interactions. Our findings will facilitate the design of therapeutic interventions aimed at addressing the widening loneliness pandemic, as well as ASD. The objective of this grant is to characterize the role of oxytocin neuron activity patterns in initiation and reinforcement of social interactions. The central hypothesis is that spiking activity in oxytocinergic neural circuits plays a critical role in spontaneous and stress-induced social engagement, and that activity in distinct oxytocinergic circuits specifically controls either initiation or reinforcement of social engagement. In our specific aims we will use automated behavioral analysis of video recordings of mice living together for days, behaviorally synchronized neuronal recordings, optogenetics and chemogenetics to determine if neuronal activity of identified oxytocin neurons predicts or tracks social interactions (AIM 1). We will use optogenetics and chemogenetics to manipulate neuronal activity of specific oxytocinergic circuits to determine if they are required for the initiation or reinforcement of affiliative interactions (AIM 2). We will test if stressful contexts increase activity in specific oxytocinergic neurons to promote engagement in affiliative social interactions, as a defensive mechanism (AIM 3). Our work will significantly contribute to the field, as it will establish mechanisms that can be therapeutically targeted to drive social engagement. The proposed research is innovative because we investigate activity patterns in neuroendocrine circuits that predict spontaneously initiated and reinforced social interactions, which has not been done before. Our results will lay the bases for novel behavioral interventions and medications that could be used to prevent the negative effects of social isolation.

参与亲密的社会互动可以预测健康和长寿。催产素， 由下丘脑的特殊神经元释放， 在亲和行为中的重要作用。然而，控制催产素活性的机制 神经元，这些神经元可能控制参与社会互动， 尚未阐明。我们的长期目标是剖析神经内分泌机制， 自愿参与亲和的社会互动。我们的研究结果将有助于设计 治疗干预，旨在解决日益扩大的孤独症流行病，以及自闭症。 这项资助的目的是描述催产素神经元活动模式在 社会互动的启动和加强。核心假设是， 催产素能神经回路在自发和应激诱导的社会性 参与，并且在不同的催产素能回路中的活性特异性地控制启动或启动 或加强社会参与。在我们的具体目标中，我们将使用自动行为 对一起生活数日的小鼠的视频记录进行分析， 记录，光遗传学和化学遗传学，以确定是否识别催产素的神经元活性 神经元预测或跟踪社会互动（AIM 1）。我们将使用光遗传学， 化学遗传学，以操纵特定催产素能回路的神经元活动， 它们是亲和相互作用（AIM 2）的起始或加强所必需的。我们将测试如果 应激环境增加特定催产素能神经元的活性， 亲密的社会互动，作为一种防御机制（目的3）。我们的工作将大大 有助于该领域，因为它将建立可以治疗靶向的机制， 推动社会参与。拟议的研究是创新的，因为我们调查活动 神经内分泌回路的模式，预测自发启动和加强社会 互动，这是以前没有做过的。我们的研究结果将为新的行为奠定基础 可用于预防社会影响的干预措施和药物 隔离