Central release of the neuropeptide oxytocin (OXT) modulates neural substrates involved in socio-affective behavior. This property has prompted research into the use of intranasal OXT administration as an adjunctive therapy for brain conditions characterized by social impairment, such as autism spectrum disorders (ASD). However, the neural circuitry and brain-wide functional networks recruited by intranasal OXT administration remain elusive. Moreover, little is known of the neuroadaptive cascade triggered by long-term administration of this peptide at the network level. To address these questions, we applied fMRI-based circuit mapping in adult mice upon acute and repeated (seven-day) intranasal dosing of OXT. We report that acute and chronic OXT administration elicit comparable fMRI activity as assessed with cerebral blood volume mapping, but entail largely different patterns of brain-wide functional connectivity. Specifically, acute OXT administration focally boosted connectivity within key limbic components of the rodent social brain, whereas repeated dosing led to a prominent and widespread increase in functional connectivity, involving a strong coupling between the amygdala and extended cortical territories. Importantly, this connectional reconfiguration was accompanied by a paradoxical reduction in social interaction and communication in wild-type mice. Our results identify the network substrates engaged by exogenous OXT administration, and show that repeated OXT dosing leads to a substantial reconfiguration of brain-wide connectivity, entailing an aberrant functional coupling between cortico-limbic structures involved in socio-communicative and affective functions. Such divergent patterns of network connectivity might contribute to discrepant clinical findings involving acute or long-term OXT dosing in clinical populations.

中文翻译：

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急性和重复鼻内催产素差异调节全脑功能连接。

神经肽催产素 (OXT) 的中枢释放调节参与社会情感行为的神经底物。这一特性促使研究使用鼻内 OXT 给药作为以社交障碍为特征的脑部疾病的辅助疗法，例如自闭症谱系障碍 (ASD)。然而，鼻内 OXT 给药招募的神经回路和全脑功能网络仍然难以捉摸。此外，对于在网络水平长期施用这种肽所触发的神经适应性级联反应知之甚少。为了解决这些问题，我们将基于 fMRI 的电路映射应用于成年小鼠急性和重复（7 天）鼻内给药 OXT。我们报告说，急性和慢性 OXT 给药引起了可比的 fMRI 活动，如通过脑血容量测绘评估的，但需要大不相同的全脑功能连接模式。具体而言，急性 OXT 给药重点增强了啮齿动物社会大脑关键边缘成分内的连通性，而重复给药导致功能连通性显着和广泛增加，涉及杏仁核和扩展皮质区域之间的强耦合。重要的是，这种连接重新配置伴随着野生型小鼠社交互动和交流的矛盾减少。我们的结果确定了外源性 OXT 管理所参与的网络底物，并表明重复的 OXT 给药导致大脑范围内连接的实质性重构，导致参与社会交流和情感功能的皮质边缘结构之间出现异常的功能耦合。