GRIN2A Mutation Linked to Impaired Belief Updating in Schizophrenia

MIT researchers describe a GRIN2A mutation—previously identified through a large-scale screen in people with schizophrenia—that was modeled in mice and associated with behavior interpreted as impaired “belief updating” on a reward-guided choice task.

Behavioral testing involved a two-lever food-reward paradigm in which the higher-reward option required progressively more effort over time. The mice learned to prefer the high-reward lever initially, then faced increasing response requirements for that option while the low-reward lever remained stable; wild-type animals adapted by switching preference near the point at which the two options offered roughly comparable “value” per unit effort. By contrast, GRIN2A-mutant mice switched later and showed more back-and-forth transitions between levers during the changing contingency.

The investigators interpret this later, less stable switching as evidence of impaired belief updating—placing greater weight on prior expectations than on accumulating new task information.

Mechanistic measurements point to the mediodorsal thalamus as the largest mutation-associated functional change observed using functional ultrasound imaging and electrical recordings. Neural activity in this region tracked the evolving relative value of the two options across the session, aligning with the task’s shifting effort–reward tradeoff.