Grant: Travel Awards - Institute Community Support

Chronic social isolation during adolescence disrupts normal social behaviour and is a risk factor for anxiety and depression. Proper social functioning during adolescence is essential for the development of adult social behaviour. Yet, our knowledge of which brain regions and circuits are affected by social isolation remains incomplete. Based on our previous work (Dawson et al., 2023), the activity of hypocretin neurons-a cluster endemic to the lateral hypothalamus that govern arousal and motivation-is essential for normative social behaviour. Our project builds on these findings to test our hypothesis that chronic social isolation produces deficits in social interaction by disrupting the normal functioning of hypocretin neurons. We first performed activity recordings from hypocretin neurons in control (group-housed) and isolated (single-housed) mice to examine differences in activity during social interaction, quantified using machine learning. Here, we show that hypocretin activity increases in both female and male control and isolated mice upon initial interaction with a same-sex stranger but that the activity amplitude is significantly diminished in both female and male isolated mice. Isolated mice also displayed deficits in social interaction compared with controls. Next, we used a novel hypocretin biosensor to examine how hypocretin signaling is altered in specific brain regions in isolated mice and in response to social fear. Our results show how chronic social isolation interacts with experiences of social fear to alter both behavioural responses and hypocretin signaling during subsequent social interactions. Finally, by modulating subgroups of hypocretin neurons, we demonstrated that distinct functional groupings of these neurons drive specific aspects of social behaviour.