Speaker: Athanasios Markopoulos (he/him), McGill University (grid.14709.3b) Title: Lysergic acid diethylamide (LSD) increases social behaviour and bursting activity in medial prefrontal cortex neurons. Emcee: B. Ezgi Arikan Backend host: Rekha Varrier Details: https://neuromatch.io/abstract?submission_id=rec2ltn2XcTmnMzGu Presented during Neuromatch Conference 3.0, Oct 26-30, 2020. Summary: Social behaviour (SB) encompasses a plethora of complex interactions among individuals. The medial prefrontal cortex (mPFC) exerts a pivotal role in the modulation of SB in mammals since mPFC dysregulation has been demonstrated to be involved in the pathogenesis of impaired SB phenotypes. In the past 15 years, psychedelic drugs have been investigated as potential therapeutics in psychiatry. Lysergic acid diethylamide (LSD) in humans has been shown, in clinical settings, to produce feelings of happiness, trust, closeness to others, and enhanced emotional empathy. Despite these positive results, the ability of LSD to modulate SB has not been investigated, and the neuronal mechanisms underlying LSD's behavioural effects remain elusive. Here, we dissected the ability of acute and repeated LSD to exert prosocial effects and to modulate neuronal activity of the mPFC in mice. We found that repeated (30ug/kg per day, for 7 days), but not acute LSD treatment significantly increased the time spent interacting with an intruder mouse in the Direct Social Interaction Test. Similarly, repeated LSD treatment increased sociability and the preference for social novelty in mice subjected to the Three-Chambers Sociability Test. These behavioural results are paralleled with our electrophysiological findings. Using in-vivo extracellular single-unit recordings, we found that acute LSD treatment had no significant effect on the spontaneous firing nor the bursting activity of mPFC neurons, but repeated LSD treatment significantly increased the bursting activity of these neurons. Ultimately, our results demonstrate the ability of LSD to produce pro-social effects that are coupled with an increase in mPFC neuronal bursting activity.