Oxytocin activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating the short- and long-term forms of social recognition memory is not fully understood. In this study, we employed a chemogenetic approach to specifically target the activity of PVH oxytocin neurons in rats and found that silencing these neurons impaired both long and short-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus, as a novel target of PVH oxytocinergic axonal projections. Furthermore, we used multiplex fluorescence in-situ hybridization and found that oxytocin receptors in the SuM are predominantly in excitatory neurons. Finally, we examined the role of the SuM in social recognition memory, by using a highly selective antagonist to block oxytocin receptors in the SuM. We found that oxytocin activity in the SuM is necessary for the formation of long- and short-term social recognition memory. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforces the specific role of PVH oxytocin neurons in regulating social recognition memory.