People with schizophrenia often have trouble using new information, which can make everyday choices feel confusing.
Scientists at MIT discovered that a small change in a gene called grin2a can break a brain circuit that helps the mind update what it knows when fresh data arrives.
The gene makes part of a receptor that responds to the chemical glutamate. When the mutation is present, the circuit does not work as fast, and thoughts stay stuck on old ideas.
"If the circuit is weak, the brain cannot quickly blend new facts with what it already believes," explained Professor Guoping Feng, a leading brain researcher at MIT.
Nature Neuroscience
Why Schizophrenia Runs in Families
About one in a hundred people develop schizophrenia. The risk jumps to ten percent if a close relative has it, and to fifty percent for identical twins.
Large studies have found more than a hundred DNA spots linked to the illness, but many sit in parts of the genome that do not code for proteins, making them hard to study.
To get clearer answers, researchers used whole‑exome sequencing, which looks only at the protein‑making sections of DNA. By comparing roughly 25,000 patients with 100,000 healthy volunteers, they highlighted ten genes that raise the chance of getting schizophrenia.
What the grin2a Change Does to the Brain
In the lab, the team gave mice a copy of the grin2a mutation. While mice cannot show hallucinations, they can reveal how well the brain handles new sensory clues.
Scientists think psychosis may stem from a brain that clings too tightly to its original belief and does not weigh fresh input enough.
"A typical brain forms a guess about reality, then updates that guess when new signals arrive. In schizophrenia, the old guess stays too strong, so the new belief drifts away from what’s real," said researcher Zhou.
Testing Decision Speed
To see this in action, Zhou set up a lever‑press game. One lever gave a small milk drop after six presses; the other gave a bigger reward with each press. At first, all mice liked the richer lever.
Later, the effort needed for the rich lever grew, while the easy lever stayed the same. Normal mice switched to the easier option once the two choices were equally hard.
Mice carrying the grin2a mutation kept swapping back and forth for a long time before finally settling on the simpler lever. Their decision‑making was noticeably slower.
The Key Brain Area
Using ultrasound imaging and electrical recordings, the researchers saw that the mutation most affected the mediodorsal thalamus. This region talks to the prefrontal cortex, forming a thalamocortical loop that guides choices and planning.
Neurons in this thalamus tracked how valuable each lever was, and they showed different activity patterns when the mice were exploring versus committing to a choice.
Turning the Circuit Back On
The team used optogenetics – a technique that makes neurons fire when light shines on them – to stimulate the affected thalamic cells. After activation, mutant mice behaved much like normal mice, choosing the efficient lever more quickly.
Only a small slice of schizophrenia patients carry a grin2a mutation, but the same thalamocortical pathway may be faulty in many others, offering a common target for future therapies.
Researchers are now hunting for drug‑friendly spots within this circuit that could restore proper decision‑making.
Funding
The work was supported by the National Institute of Mental Health and several MIT research centers, including the Poitras Center, the Yang Tan Collective, and the Stanley Center for Psychiatric Research.