The Function Of The Medial Prefrontal Cortical Inhibitory Neurons In The Modulation Of Social Interaction Behavior

Social interaction is a complex behavior essential for many species and is observed in species as simple as single-celled microorganisms to species as complex as humans and is vital to the survival and reproduction of microorganisms and animals.Social dysfunction is strongly associated with autism,schizophrenia,depression,and social anxiety disorder in clinical.Therefore,understanding the neural mechanism of social interaction behavior is of great significance to reveal the pathogenesis of social disorder.Previous studies have found that the medial prefrontal cortex(m PFC)plays a crucial role in social behavior.A disturbed excitatory and inhibitory balance in the cortex has shown to induce social dysfunction.Increasing the inhibitive effect of cortex reduces the time of social interaction.Cortical inhibition mediated by diverse GABAergic interneurons,which have high diversity in morphology,molecular markers,electrophysiological characteristics and synaptic connections.These studies suggest that different types of inhibitory neurons may play different roles in processing information.The functional contributions of different IN subtypes remain unknown.In particular,it is unclear how distinct interneuron subtypes behave during real-time interactions and what kind of activities they generated are important for appropriate social interactions.We use in vivo multi-channel recording,immunohistochemistry,pharmacogenetic and optogenetics to explore the above questions,found distinct activity patterns and manipulation effects of two major populations of prefrontal INs,parvalbumin(PV)and somatostatin(SST)INs in mice social interaction.Specifically,social interaction closely correlated with spiking of PV but not SST INs and selectively increased low gamma but not high gamma rhythms.Furthermore,pharmacogenetic inactivation of PV instead of SST INs decreased low gamma power and impaired sociability.However,interestingly,optogenetic synchronization of either PV or SST INs at low gamma frequency produced pro-social effects,whereas high gamma frequency stimulation of PV INs enhances high gamma rhythms but had no effect.These results reveal distinct roles of PV and SST INs in social interaction with a critical dependence on low-gamma rhythms.Moreover,except for PV INs,SST INs could serve as therapeutic targets for social improvement in major neuropsychiatric disorders.These results reveal a functional differentiation among IN subtypes and suggest the importance of low gamma rhythms in social interaction behavior.Furthermore,our findings underscore previously unrecognized potential of SST INs as therapeutic targets for social impairments commonly observed in major neuropsychiatric disorders.