Unveiling the Impact of Ventral Hippocampal Astrocyte Signaling on Socio-Sexual Behavior in Mice – SOCIALYTE

Astrocytes are not merely “nurturing” cells for neurons but instead crucial regulators of neuronal activity. They display tailored interactions with neurons in a brain region-specific manner and thus regulate a wide range of behaviors including olfaction, food intake or learning. Surprisingly, the role of astrocytes in brain regions associated with social behaviors remains mostly unknown.
Interplay between the immune and the central nervous system has mainly been described in disease. More recent evidence indicates that, even in the absence of pathological signals, cytokines can act as neuromodulators and regulate physiological behaviors. Interestingly, cytokines such as interferon gamma (IFN-?) act through the ubiquitous JAK-STAT signaling to regulate social behavior. In astrocytes, the JAK-STAT pathway has exclusively been studied in pathological conditions, as it is a master regulator of neuroinflammation but whether it can also regulate social behavior remains unknown.

Our preliminary results show that social interaction with a novel mouse activates astrocyte JAK-STAT signaling in the mouse ventral hippocampus (vHPC). Furthermore, replicating this activation specifically in vHPC astrocytes using a constitutively active form of JAK2 promotes socio-sexual preference in male mice. This project aims at deciphering how the JAK-STAT signaling in hippocampal astrocytes promotes socio-sexual behavior in mice. To do so, we will combine viral-mediated targeting of astrocytes and neurons, in vivo and ex vivo functional studies and mouse behavior. This project suggests an unexpected role for astrocyte JAK-STAT pathway as a dual regulator of cytokine signaling and social behavior in mice. It will provide crucial insights into the emerging topic of cytokine-induced regulation of physiological behaviors and potentially discovering novel therapeutic candidates for neurological disorders.