The PVN-to-MeA Oxytocinergic Pathway Encodes Social Relationship-Dependent Consolation Behavior in Mandarin Voles

Consolation behavior is defined as an increase in affiliative contact toward a distressed individual and is associated with the physical and emotional well-being of social species. Allogrooming a distressed individual represents a primary form of consolation behavior and is considered as a complex type of empathy. However, the neural mechanisms underlying allogrooming remain poorly understood. In this study, using adult male and female monogamous mandarin voles (Lasiopodomys mandarinus, approximately three-month-old), we demonstrate that individuals exhibited significantly more allogrooming toward a defeated same-sex littermate than toward a defeated stranger, indicating effects of familiarity on consolation. Social interaction with a defeated cagemate elicited more activity of paraventricular nucleus of the hypothalamus (PVN) neurons, medial amygdala (MeA) and PVN oxytocin (OT) neurons compared to interaction with a stranger male. Using cholera toxin subunit B (CTB) as a retrograde tracer, we confirmed that PVN OT neurons project to the MeA. Fiber photometry recording revealed that the activity of both PVN OT neurons projecting to MeA and OTR-expressing neurons in the MeA was significantly elevated during allogrooming a defeated cagemate. Furthermore, in both male and female voles, overexpression of oxytocin receptor (OTR) mRNA in the MeA increased allogrooming time toward a defeated stranger, whereas interference of OTR mRNA expression in the MeA significantly reduced allogrooming toward a defeated cagemate. These findings demonstrate that mandarin voles display different levels of allogrooming toward distressed siblings or strangers and reveal a critical role for the PVN-to-MeA oxytocinergic pathway in encoding and modulating allogrooming behavior.