MIT neuroscientists identified a gene mutation, found in some patients with schizophrenia, that impairs the function of a brain circuit responsible for updating beliefs based on new input.

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MIT neuroscientists identified a mutation in the grin2a gene — which encodes part of the NMDA receptor — that impairs a thalamocortical brain circuit responsible for updating beliefs based on new sensory input. Using mouse models, researchers showed that animals with this mutation struggle to adapt decisions in changing reward environments, mirroring cognitive impairments seen in schizophrenia patients. The mediodorsal thalamus was identified as the most affected region, and optogenetic activation of its neurons reversed the behavioral deficits. While only a small fraction of schizophrenia patients carry grin2a mutations, the circuit dysfunction may represent a shared mechanism across a broader subset of patients, pointing toward potential drug targets.

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