Neural Circuits That Regulate Social Motivation in Autism

自闭症谱系障碍(ASD)以社会障碍为特征，包括社会认知障碍， 社会认知和社会关注。最近，人们越来越有兴趣研究 自闭症患者社会功能的激励机制。所谓的“社会动机” ASD的假说是，支持社会动机的大脑回路的功能障碍可能构成 自闭症的一种原发缺陷，可能对社会认知的发展产生下游影响。这个 中脑边缘多巴胺系统位于腹侧被盖区并投射至核团 伏隔(NAC)是表达多种形式的动机行为的重要底物。人类 神经成像研究表明，ASD患者的中脑边缘激活减少了对社会的回报，提示 中脑边缘多巴胺能系统功能的降低可能是社会动机降低的原因。 ASD.虽然自闭症的社会缺陷可能与病理性的中脑边缘多巴胺系统活动有关，但它是 未知的如果精确的神经回路操作，可以直接控制NAC中的多巴胺输出，以促进 ASD动物模型中的亲社会行为。此外，神经肽催产素(OT)是一种很有前途的 治疗促进ASD的社会参与，并已知调节VTA活动以响应社会 特别是奖励。然而，OT神经元调节VTA的功能神经回路 多巴胺能活性尚未确定。这些都是我们对神经的理解中的关键差距 CII-控制受激励的社交活动的文化。我们提出了一个整合光伏发电的翻译项目 ASD小鼠模型中的电路操作及其临床功能神经成像效果评估 在ASD患者的奖赏回路上的OT。

Autism spectrum disorder (ASD) is characterized by social impairments, including impaired social cognition, social percepfion, and social attention. Recently, there has been increased interest in examining the impact of motivational systems on social functioning in ASD. The frarinework of the so-called "social motivation hypothesis" of ASD is that functional disruption in brain circuits that support social motivational may constitute a primary deficit in ASD that may have downstream effects on the development of social cognition. The mesolimbic dopamine system arising in the ventral tegmental area (VTA) and projecfing to the nucleus accumbens (NAc) is an essential substrate for the expression of many forms of motivated behaviors. Human neuroimaging studies have demonstrated reduced mesolimbic activation in ASD to social rewards, suggesting that reduced function of the mesolimbic dopaminergic system may underlie decreased sociial motivation in ASD. Whereas social deficits in ASD may be related to pathological mesolimbic dopamine system activity, it is unknown if precise neural circuit manipulations that can directly control dopamine output in the NAc to promote pro-social behaviors in animal models of ASD. In addition, the neuropeptide oxytocin (OT) is a promising therapeufic to promote social engagement in ASD and is known to regulate VTA activity in response to social rewards specifically. However the functional neural circuitry by which OT neurons regulate VTA dopaminergic activity has not been identified. These are critical gaps in our understanding of the neural cii-cuitry that controls motivated social engagement. We propose a translational project integrating optogenetic circuit manipulafions in a mouse model of ASD with a clinical functional neuroimaging evaluation of the effects of OT on reward circuits in individuals with ASD.