Calcium Dynamics in Hypothalamic Paraventricular Oxytocin Neurons and Astrocytes Associated with Social and Stress Stimuli.

Activation of hypothalamic paraventricular oxytocin (OXT) neurons by social or stress stimuli triggers OXT release to promote social investigation and buffer adverse effects of stress, respectively. Astrocytes, a type of glial cells, can bidirectionally interact with hypothalamic neurons to participate in local activity regulation within the paraventricular nucleus (PVN). It remains unknown whether contextual factors related to stimuli, as well as biological factors such as sex, influence OXT neuronal or astrocyte activity and/or their interactions. To address this question, we performed dual-color fiber photometry in freely behaving male and female mice to simultaneously record Ca dynamics in OXT neurons and astrocytes during acute social (i.e., interactions with familiar vs. unfamiliar conspecifics) and stress (i.e., looming shadow) stimuli. During social stimuli, we observed the most pronounced Ca changes in OXT neurons in females, revealing sex and familiarity context specificity. No astrocyte Ca changes were detected in either sex regardless of conspecific familiarity. In contrast, looming shadow stress increased Ca in both OXT neurons and astrocytes in both sexes during an active escape ("run") strategy. Ca level changes in OXT neurons and astrocytes were significantly correlated during social investigations in both sexes regardless of conspecific familiarity. During looming shadow, this functional coupling was only observed in females during active escape. Together, our results suggest that sex, context, and behavioral strategy serve as major factors that shape the activity of OXT neurons and astrocytes, as well as their functional coupling, to potentially aid the adaptive response to social or stress stimuli.