Functional ontogeny of pair bonding neural circuits

项目摘要/摘要 我们在成年后建立的有益的纽带，特别是我们与浪漫伴侣之间的情侣纽带，有无数的 对我们的大脑和行为的保护作用。在社会参与和能力方面有困难的个人，如 由于患有社交焦虑症、严重抑郁症、多动症或自闭症谱系障碍的人， 容易受到社会孤立和贫困社交网络的健康风险的影响。多巴胺能神经元的异常活动 青春期的奖赏系统与许多此类疾病的发生相吻合，这表明发育 促进社会回报的神经底物的异常是疾病病理的基础。关键的是，大多数 我们知道促进配对结合的神经机制来自对成年人大脑的研究，强调了一个 迫切需要研究社会联系回路的功能发展，以设计更好的治疗方法 针对社交功能障碍。目前的提案旨在利用社会一夫一妻制的草原田鼠制度来 研究启动配对结合能力的多巴胺能奖赏回路的成熟变化 成人期。草原田鼠与它们的配偶形成强大的配对联系，这依赖于多巴胺的功能活动 系统。在目标1中，我将使用纤维光度法来询问发育年龄和性别如何调节社会诱导的变化 体内的多巴胺能神经活性。在目标2中，我将使用化学遗传学的方法来研究 敏感发育期的多巴胺回路会影响成人配对结合的表型。最后，在《目标3》中我将 研究同性和异性社交活动转录特征的发育变化 草原田鼠成熟后能够依赖多巴胺进行配对结合。总之，这些努力将决定 不同发育时期的社会经历是如何为配对结合多巴胺回路的成熟奠定基础的。这些 这些发现将为神经精神病学中可能被破坏的分子和细胞过程提供新的见解 涉及粘合行为受损的疾病，这在传统的非粘合啮齿动物模型中无法进行研究。

Project summary/Abstract The rewarding bonds we forge in adulthood, in particular our pair bonds with romantic partners, have innumerable protective effects on our brains and behaviors. Individuals with difficulties in social engagement and competence, such as those suffering from social anxiety, major depression, ADHD, or Autism Spectrum Disorder, are particularly susceptible to the health risks of social isolation and impoverished social networks. Aberrant activity of dopaminergic reward systems during adolescence coincides with the onset of many of these disorders, suggesting that developmental abnormalities in the neural substrates that promote social reward underlies disease pathology. Critically, most of what we know about the neural mechanisms that facilitate pair bonding come from the study of adult brains, highlighting a dire need to investigate the functional development of social bonding circuits to design better therapeutic treatments for social dysfunctions. The current proposal aims to leverage the socially monogamous prairie vole system to investigate the maturational changes in dopaminergic reward circuitry that initiate the capacity for pair bonding in adulthood. Prairie voles form strong pair bonds with their mates, which relies on the functional activity of dopamine systems. In Aim 1, I will use fiber photometry to ask how developmental age and sex mediates socially induced changes in in vivo dopaminergic neural activity. In Aim 2, I will use chemogenetic approaches to investigate how perturbing dopamine circuits during sensitive developmental periods impacts adult pair bonding phenotypes. Finally, in Aim 3 I will investigate the developmental changes in transcriptional signatures of same‐sex and opposite‐sex social interactions as prairie voles mature and become capable of dopamine‐dependent pair bonding. Altogether, these efforts will determine how social experiences across developmental time scaffold the maturation of pair bonding dopamine circuits. These findings will profer novel insights into the molecular and cellular processes that may be disrupted in neuropsychiatric illnesses involving impaired bonding behaviors, which cannot be investigated in traditional non‐bonding rodent models.