Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression

Woosuk Chung; Su Yeon Choi; Eunee Lee; Haram Park; Jaeseung Kang; Hanwool Park; Yeonsoo Choi; Dongsoo Lee; Sae-Geun Park; Ryunhee Kim; Yi Sul Cho; Jeonghoon Choi; Myoung-Hwan Kim; Jong Won Lee; Seungjoon Lee; Issac Rhim; Min Whan Jung; Daesoo Kim; Yong Chul Bae; Eunjoon Kim

doi:10.1038/nn.3927

Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression

Nat Neurosci. 2015 Mar;18(3):435-43. doi: 10.1038/nn.3927. Epub 2015 Jan 26.

Authors

Woosuk Chung¹, Su Yeon Choi², Eunee Lee³, Haram Park², Jaeseung Kang², Hanwool Park¹, Yeonsoo Choi², Dongsoo Lee³, Sae-Geun Park², Ryunhee Kim², Yi Sul Cho⁴, Jeonghoon Choi², Myoung-Hwan Kim⁵, Jong Won Lee³, Seungjoon Lee², Issac Rhim³, Min Whan Jung⁶, Daesoo Kim², Yong Chul Bae⁴, Eunjoon Kim⁶

Affiliations

¹ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
² Department of Biological Sciences, KAIST, Daejeon, Korea.
³ Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.
⁴ Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
⁵ 1] Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. [2] Seoul National University Bundang Hospital, Gyeonggi, Korea.
⁶ 1] Department of Biological Sciences, KAIST, Daejeon, Korea. [2] Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Korea.

PMID: 25622145
DOI: 10.1038/nn.3927

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Case-Control Studies
Cells, Cultured
Excitatory Amino Acid Antagonists / pharmacology
Excitatory Amino Acid Antagonists / therapeutic use
Exploratory Behavior / drug effects
Exploratory Behavior / physiology
Feeding Behavior / drug effects
Feeding Behavior / physiology
Gene Expression Regulation / drug effects
Gene Expression Regulation / physiology*
Grooming / drug effects
Grooming / physiology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation / genetics*
Nerve Tissue Proteins / genetics*
Neurons / drug effects
Neurons / physiology
Neurons / ultrastructure
Receptor, Metabotropic Glutamate 5 / metabolism*
Receptors, N-Methyl-D-Aspartate / metabolism*
Recognition, Psychology / drug effects
Recognition, Psychology / physiology
Social Behavior Disorders / drug therapy
Social Behavior Disorders / genetics*
Vocalization, Animal / drug effects
Vocalization, Animal / physiology

Substances

Baiap2 protein, mouse
Excitatory Amino Acid Antagonists
Nerve Tissue Proteins
Receptor, Metabotropic Glutamate 5
Receptors, N-Methyl-D-Aspartate