title: Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression.
abstract: Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53(-/-) mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Woosuk
authors.initials: W
authors.lastname: Chung
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Eunee
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Haram
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Kang
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Hanwool
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Sae-Geun
authors.initials: SG
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Ryunhee
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Yi Sul
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Jeonghoon
authors.initials: J
authors.lastname: Choi
authors.affiliation: 1] Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. [2] Seoul National University Bundang Hospital, Gyeonggi, Korea.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Issac
authors.initials: I
authors.lastname: Rhim
authors.affiliation: 1] Department of Biological Sciences, KAIST, Daejeon, Korea. [2] Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Min Whan
authors.initials: MW
authors.lastname: Jung
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.affiliation: 1] Department of Biological Sciences, KAIST, Daejeon, Korea. [2] Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016022:Case-Control Studies; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012920:Social Behavior Disorders / Q000188:drug therapy / Q000235:genetics*; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology
chemical_list: C539986:Baiap2 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D064529:Receptor, Metabotropic Glutamate 5; D016194:Receptors, N-Methyl-D-Aspartate