Lee, Eunee Lee, Seungjoon Shin, Jae Jin Choi, Woochul Chung, Changuk Lee, Suho Kim, Jihye Ha, Seungmin Kim, Ryunhee Yoo, Taesun Yoo, Ye-Eun Kim, Jisoo Noh, Young Woo Rhim, Issac Lee, Soo Yeon Kim, Woohyun Lee, Taekyung Shin, Hyogeun Cho, Il-Joo Deisseroth, Karl Kim, Sang Jeong Park, Joo Min Jung, Min Whan Paik, Se-Bum Kim, Eunjoon 2024-01-19T14:02:52Z 2024-01-19T14:02:52Z 2022-01-10 2021-08 2041-1723 https://pubs.kist.re.kr/handle/201004/116624 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. How NMDAR and GABA neuronal dysfunctions result in impaired social behaviour is unclear. Here, the authors show that NMDARs and gap junctions in cortical PV interneurons modulate burst firing, affecting social behaviour. English Nature Publishing Group Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice Article 10.1038/s41467-021-25356-2 1 Nature Communications, v.12, no.1 Nature Communications 12 1 Y scie scopus 000691022000014 2-s2.0-85113368000 Multidisciplinary Sciences Science & Technology - Other Topics Article ELECTRICAL SYNAPSES PARVALBUMIN NEURONS PREFRONTAL CORTEX NMDA RECEPTORS AUTISM INTERNEURONS INFORMATION DYSFUNCTION DEFICITS ROLES