Researchers at Japan's Okinawa Institute of Science and Technology (OIST) have identified a brain chemical that helps animals abandon old habits the moment they stop working. Watching mice navigate a virtual-reality maze, the team found that when an expected reward suddenly failed to appear, the brain released a surge of the neurotransmitter acetylcholine — and the bigger the surge, the more likely the mouse was to switch strategies.
Using two-photon microscopy to watch brain activity in real time, the scientists saw acetylcholine spike at the exact moment of disappointment, pushing the mice toward 'lose-shift' behavior — changing their choice after a failed attempt. When the researchers blocked the chemical, the animals became rigid, stubbornly sticking with outdated routes even as they kept failing.
The findings, published in Nature Communications, cast acetylcholine as a key signal for behavioral flexibility and could help explain disorders marked by rigid, repetitive behavior, from addiction to obsessive-compulsive disorder. The authors say understanding how the brain knows when to let go of a habit is a first step toward treatments that restore that flexibility.