Neuroendocrine circuits for engagement in affiliative social interactions

参与社交活动预示着健康和长寿。荷尔蒙催产素， 它是由下丘脑中的特殊神经元释放的，已被证明在 在从属行为中扮演重要角色。然而，控制催产素活性的机制 神经元，这些神经元可能通过它来控制社会互动的参与， 尚未被阐明。我们的长期目标是剖析神经内分泌驱动机制 自愿参与从属社交活动。我们的发现将有助于设计 旨在解决日益扩大的孤独流行病以及自闭症的治疗干预措施。 这项资助的目的是描述催产素神经元活动模式在脑内的作用。 启动和加强社会互动。中心假设是尖峰活动 催产素能神经回路在自发和应激诱导的社交中起着关键作用 参与，而不同催产素能回路中的活动特定地控制着 或加强社会参与度。在我们的具体目标中，我们将使用自动行为 小鼠共同生活数日的行为同步化神经元录像分析 记录、光遗传学和化学遗传学确定已识别的催产素的神经元活性 神经元预测或跟踪社会互动(目标1)。我们将使用光遗传学和 化学遗传学操纵特定催产素能回路的神经元活动以确定是否 它们是发起或加强附属机构互动所必需的(目标2)。我们将测试是否 应激环境增加特定催产素能神经元的活性以促进参与 附属社会互动，作为防御机制(目标3)。我们的工作将极大地 为这一领域作出贡献，因为它将建立能够在治疗上有针对性的机制 推动社会参与。拟议的研究是创新的，因为我们调查的是活动 神经内分泌回路中预测自发启动和强化社会的模式 互动，这是以前从未做过的。我们的研究结果将为新的行为学研究奠定基础 干预措施和药物，可以用来预防社会的负面影响 与世隔绝。

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.