Eunee Lee1,2,10, Seungjoon Lee3,10, Jae Jin Shin4,5,10, Woochul Choi6,10, Changuk Chung1, Suho Lee3, Jihye Kim1, Seungmin Ha1, Ryunhee Kim1, Taesun Yoo1, Ye-Eun Yoo3, Jisoo Kim3, Young Woo Noh3, Issac Rhim1, Soo Yeon Lee3, Woohyun Kim3, Taekyung Lee1, Hyogeun Shin7, Il-Joo Cho7, Karl Deisseroth8, Sang Jeong Kim9, Joo Min Park5,*, Min Whan Jung1,3,*, Se-Bum Paik6,* & Eunjoon Kim1,3,*
1Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea. 2Department of Anatomy, College of Medicine, Yonsei University, Seoul, Korea. 3Department of Biological Sciences, KAIST, Daejeon, Korea. 4Department of Brain and Cognitive Science, College of Natural Science, Seoul National University, Seoul, Korea. 5Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Korea. 6Program of Brain and Cognitive Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, Korea. 7Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea. 8Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. 9Department of Physiology, College of Medicine, Seoul National University, Seoul, Korea. 10These authors contributed equally: Eunee Lee, Seungjoon Lee, Jae Jin Shin, Woochul Choi.
NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2–/– mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2–/– Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2–/– Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2–/– mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.