Scientists at MIT have identified a gene mutation that disrupts a brain circuit involved in updating beliefs and adapting to new information. The mutation occurs in the grin2a gene, previously linked to schizophrenia in large genetic studies. The findings suggest that targeting this circuit could eventually help improve cognitive function in some patients.
Researchers analyzed genetic data from approximately 25,000 people with schizophrenia and 100,000 without, identifying 10 genes where mutations significantly raise risk. The grin2a gene helps form part of the NMDA receptor, which plays a central role in brain signaling and learning. To understand how the mutation affects behavior, researchers engineered mice with the same genetic change. While mice cannot experience hallucinations or delusions, they can model related problems such as difficulty adjusting to new information. In a decision-making task, healthy mice adapted when the effort required to obtain a larger reward increased, switching to the easier option. Mice with the grin2a mutation struggled, switching back and forth and taking much longer to settle on the better choice.
The researchers traced the problem to the mediodorsal thalamus, a brain region that connects to the prefrontal cortex and supports decision-making and flexible thinking. Neurons in this region track the value of each option, helping guide choices. In a striking result, using optogenetics to activate neurons in the mediodorsal thalamus made mice behave more like normal mice, suggesting the circuit plays a direct role in the symptoms. The study, published in Nature Neuroscience on March 18, indicates that while only a small percentage of schizophrenia patients carry grin2a mutations, this circuit may represent a shared pathway that contributes to cognitive impairment across different forms of the disorder.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://scitechdaily.com/scientists-discover-why-the-brain-gets-stuck-in-schizophrenia/