Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice

Highlights

• Gamma and theta oscillation synchrony in mPFC is crucial for social behavior

• Principal neuron encoding dysfunction in mPFC is associated with social deficits

• Decreased FS IN excitability in mPFC is a causative factor in NL3-R451C KI mice

• Patterned optogenetic stimulation of mPFC PV INs rescues social deficit in KI mice

Summary

Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.