PVN AVP neurons projecting to MeA modulate social recognition and anxiety-like behavior in female mice

Arginine vasopressin (AVP) is well established in regulating social cognition and emotional responses in males. However, its roles in these processes in females and the underlying circuit mechanisms, remain poorly understood. In this study, female mice spent significantly more time sniffing the anogenital region of unfamiliar conspecifics compared to familiar individuals. Fiber photometry recordings revealed that the calcium activity in paraventricular nucleus of the hypothalamus (PVN) AVP neurons was elevated when sniffing unfamiliar mice relative to familiar ones. No significant differences were observed during non-social exploratory behaviors such as bedding sniffing or self-grooming, indicating a specific involvement of these neurons in social investigation. Retrograde tracing using cholera toxin B (CTB) confirmed direct projections from AVP neurons in the PVN to the medial amygdala (MeA). Chemogenetic inhibition of the PVN-MeA AVPergic pathway impaired social recognition and reduced anxiety-like behaviors. Furthermore, bilateral microinjection of the V1a receptor (V1aR) antagonist into the MeA decreased both anxiety-like behaviors and social investigation toward unfamiliar mice. These findings demonstrate that the AVPergic projection from the PVN to the MeA modulates social cognition and emotional state in female mice, providing a circuit mechanism for social and affective dysregulation and offering potential targets for the treatment of related neuropsychiatric disorders.