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

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 me...

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Published in:Neuron (Cambridge, Mass.) Mass.), 2018-03, Vol.97 (6), p.1253-1260.e7
Main Authors: Cao, Wei, Lin, Shen, Xia, Qiang-qiang, Du, Yong-lan, Yang, Qian, Zhang, Meng-ying, Lu, Yi-qing, Xu, Jing, Duan, Shu-min, Xia, Jun, Feng, Guoping, Xu, Junyu, Luo, Jian-hong
Format: Article
Language:English
Subjects:
Autism
Behavior
Brain
Excitability
Firing pattern
gamma oscillation
Hyperactivity
Interneurons
mPFC
Mutation
Neural coding
Neuroligin 3
Neurons
optogenetic stimulation
Parvalbumin
Prefrontal cortex
PV interneuron
Rodents
Social interaction
Social interactions
social novelty
Synaptogenesis
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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. •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 Cao et al. demonstrated FS interneuron deficits and gamma oscillation dysfunction in the mPFC of NL3-R451C KI mice, and the social novelty defect in the KI mice rescued by optogenetic stimulation of the PV interneurons in a theta-gamma nested pattern.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2018.02.001