Brain circuit needed to incorporate new information may be linked to schizophrenia

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"... MIT neuroscientists have now identified a gene mutation that appears to give rise to this type of difficulty. In a study of mice, the researchers found that the mutated gene impairs the function of a brain circuit that is responsible for updating beliefs based on new input.

This mutation, in a gene called grin2a, was originally identified in a large-scale screen of patients with schizophrenia. The new study suggests that drugs targeting this brain circuit could help with some of the cognitive impairments seen in people with schizophrenia. ...

More recently, researchers ... used a different strategy, known as whole-exome sequencing, to reveal gene mutations linked to schizophrenia. This technique sequences only the protein-coding regions of the genome, so it can reveal mutations that are located in known genes.

Using this approach on about 25,000 sequences from people with schizophrenia and 100,000 sequences from control subjects, the researchers identified 10 genes in which mutations significantly increase the risk of developing schizophrenia. ..."

From the 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."

Brain circuit needed to incorporate new information may be linked to schizophrenia | MIT News | Massachusetts Institute of Technology "Impairments of this circuit may help to explain why some people with schizophrenia lose touch with reality."

Reduced mediodorsal thalamus activity underlies aberrant belief dynamics in a genetic mouse model of schizophrenia (no public access)