Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice
Eunee Lee, Seungjoon Lee, Jae Jin Shin, Woochul Choi, Changuk Chung, Suho Lee, Jihye Kim, Seungmin Ha, Ryunhee Kim, Taesun Yoo, Ye-Eun Yoo, Jisoo Kim, Young Woo Noh, Issac Rhim, Soo Yeon Lee, Woohyun Kim, Tae Kyung Lee, Hyogeun Shin, Il‐Joo Cho, Karl Deisseroth, Sang Jeong Kim, Joo Min Park, Min Whan Jung, Se‐Bum Paik, Eunjoon Kim
Abstract
Abstract 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.