Anterior cingulate cortex-related functional hyperconnectivity underlies sensory hypersensitivity in Grin2b-mutant mice.

Autor: Lee S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.; Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Korea., Jung WB; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea.; Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu, 41062, Korea., Moon H; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea., Im GH; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea., Noh YW; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea., Shin W; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea., Kim YG; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea., Yi JH; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea., Hong SJ; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea.; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Korea., Jung Y; Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Korea., Ahn S; Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Korea., Kim SG; Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Korea. seonggikim@skku.edu.; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Korea. seonggikim@skku.edu.; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Korea. seonggikim@skku.edu., Kim E; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. kime@kaist.ac.kr.; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, 34141, Korea. kime@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Oct; Vol. 29 (10), pp. 3195-3207. Date of Electronic Publication: 2024 May 04.
DOI: 10.1038/s41380-024-02572-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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