Seminar: Alicja Puscian: Neural circuits for social bonding – the role of diverse cell types in the prelimbic cortex

Abstract: Neural circuits for social bonding - the role of diverse cell types in the prelimbic cortex Impairments in social interactions are a key feature of many neurodevelopmental disorders. Additionally, with progressively universal internet access well-industrialized world has been undergoing the "intimacy crisis" as real-life relationships have been replaced by their online substitutes. Now more than ever, understanding brain mechanisms underlying attachment and social bonding, seems crucial for our ability to address those aggravating health issues. As studies indicate a crucial role of the prefrontal cortex in social attachment, we investigated the contributions of the major excitatory and inhibitory cell types in its prelimbic part (PL) to this process. To increase the ecological validity of our research we tested the behavior of group-housed mice in automated assays, which closely follow murine ethology. Using transgenic mice and the Pharmacologically Selective Actuator Module-based ultrapotent chemogenetic approach, we performed time-constrained manipulation of the pyramidal neurons, parvalbumin- (PV), somatostatin-, and vasoactive intestinal peptide-expressing inhibitory cells in the PL and tested subjects' voluntary social behavior. We show that activation of the PV neurons in the PL selectively impairs animals' sociability expressed towards familiar conspecifics. Specifically, it reduces spontaneous social interactions with cagemates, diminishes animals' interest in familiar social olfactory stimuli, and decreases the time mice spend together after separation. However, such manipulation of neuronal activity neither alters the exploration of novel social stimuli nor does it impact social learning about aversive or appetitive stimuli. Taken together, our findings indicate distinctive neural mechanism influencing bonding with familiar conspecifics, but not other forms of social behavior. Notably, manipulation of other tested cell types does not lead to such distinctive social behavioral changes. Thus, our research reveals a specific role of the PV-expressing cells in the PL in the maintenance of the social structure and in sustaining ongoing interest in familiar conspecifics. The presented data lays a foundation for understanding the neural underpinnings of social attachment.