Thalamic circuits for independent control of prefrontal signal and noise

Interactions between the mediodorsal thalamus and prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision making1, but the precise mechanisms are unknown. Here, we identified two distinct mediodorsal projections to prefrontal cortex that play complementary mechanistic roles in decision making under uncertainty. Specifically, we found that a dopamine receptor (D2) expressing projection amplifies prefrontal signals when task inputs are sparse and a kainate receptor (GRIK4) expressing projection that suppresses prefrontal noise when task inputs are dense but conflicting. Collectively, our data point to distinct brain mechanisms for handling uncertainty due to low signals versus high noise, while also providing a mechanistic entry point for correcting decision-making abnormalities in disorders with a prominent prefrontal component2–6.