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조회268

기초과학연구원, 성균관대학교

Mol. Psychiatr., May 04 2024, | https://doi.org/10.1038/s41380-024-02572-y Anterior cingulate cortex-related functional hyperconnectivity underlies sensory hypersensitivity in Grin2b-mutant mice

Soowon Lee^1,2,10, Won Beom Jung^3,4,10, Heera Moon^5,10, Geun Ho Im³, Young Woo Noh⁶, Wangyong Shin⁶, Yong Gyu Kim⁶, Jee Hyun Yi⁶, Seok Jun Hong^3,7, Yongwhan Jung⁸, Sunjoo Ahn⁸, Seong-Gi Kim^3,7,9 and Eunjoon Kim^5,6

¹Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

²Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

³Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon 16419, Korea.

⁴Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu 41062, Korea.

⁵Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

⁶Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 34141, Korea.

⁷Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

⁸Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea.

⁹Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon 16419, Korea.

¹⁰These authors contributed equally:Soowon Lee, Won Beom Jung, Heera Moon.

Corresponding authors

Correspondence to Seong-Gi Kim or Eunjoon Kim.

Abstract

Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms are poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated in ASD, but whether GRIN2B mutations lead to sensory abnormalities remains unclear. Here, we report that Grin2b-mutant mice show behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). Grin2b-mutant mice with a patient-derived C456Y mutation (Grin2b ^C456Y/+) show sensory hypersensitivity to mechanical, thermal, and electrical stimuli through supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions. ACC pyramidal neurons show increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity. These results suggest that GluN2B critically regulates ASD-related cortical connectivity and sensory brain functions.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-07)
연구진국내 연구진
분야 생명과학 > 생리학

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