2026-03-18 マサチューセッツ工科大学（MIT）
MIT researchers have identified neurons in the mediodorsal thalamus (labeled pink) whose dysfunction can lead to impairments in the ability to update beliefs based on new information.Credit: Courtesy of the researchers
＜関連情報＞
- https://news.mit.edu/2026/brain-circuit-incorporates-new-information-may-be-linked-schizophrenia-0318
- https://www.nature.com/articles/s41593-026-02237-9
視床内側背側部の活動低下は、統合失調症の遺伝子改変マウスモデルにおける異常な信念ダイナミクスの根底にある Reduced mediodorsal thalamus activity underlies aberrant belief dynamics in a genetic mouse model of schizophrenia
Tingting Zhou,Yi-Yun Ho,Nolan D. Hartley,Ray X. Lee,Amanda B. Fath,Kathleen He,Xun Yuan,Sam Merrow,Jonathan Scott,Navdeep Bajwa,Jonathan Wilde,Xian Gao,Cui Li,Evan Hong,Zhanyan Fu,Matthew R. Nassar,Ralf D. Wimmer,Tarjinder Singh,Michael M. Halassa & Guoping Feng
Nature Neuroscience Published:18 March 2026
DOI:https://doi.org/10.1038/s41593-026-02237-9
Abstract
Belief updating is thought to be impaired in schizophrenia, leading to delusions. The neural substrates underlying belief updating are unknown, in part due to a lack of appropriate animal models and behavior readouts. We generated mice bearing a schizophrenia-associated point mutation in Grin2a (Grin2aY700X+/−) and developed a computationally trackable foraging task to assess belief-driven decision strategies in mice. Grin2aY700X+/− mice performed less optimally than their wild-type (WT) littermates, due to unstable cognitive states related to noisy representation of dynamic task values. We identified the mediodorsal (MD) thalamus as being hypofunctional in Grin2aY700X+/− mice and showed that MD neurons encode dynamic task values and cognitive states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/− mice and enhancing MD activity rescued task deficits in Grin2aY700X+/− mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction and a potential target for future therapeutics.
