Acute and Repeated Intranasal Oxytocin Differentially Modulate Brain-wide Functional Connectivity. (1st October 2020)

• Record Type: Journal Article
• Authors: Pagani, Marco; De Felice, Alessia; Montani, Caterina; Galbusera, Alberto; Papaleo, Francesco; Gozzi, Alessandro
• Is Part Of: Neuroscience. Volume 445(2020)
• Page Start: 83
• Page End: 94
• Publication Date: 2020-10-01
• Subjects: ASD autism spectrum disorders -- FWE familywise error -- OXT oxytocin -- rCBV relative cerebral blood volume -- USVs ultrasonic vocalizations -- VOIs volumes of interest; fMRI -- mouse -- amygdala -- connectivity -- autism -- ASD; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.12.036
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: We mapped functional connectivity changes produced by intranasal oxytocin in the mouse brain. Acute oxytocin administration enhances functional connectivity within key limbic components of the rodent social brain. Chronic oxytocin treatment reconfigures functional connectivity, leading to aberrant cortical-amygdaloid coupling. This connectional reconfiguration is associated with a paradoxical reduction in social interaction and communication. Abstract: 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.