Researchers at OIST found that when mice unexpectedly lost an anticipated reward, a surge of acetylcholine in the striatum predicted whether they would abandon the learned route and try alternatives. Using two-photon microscopy in a virtual-maze task, the team showed the cholinergic surge occurred only after an expectation was violated, not during early training errors. Chemogenetic suppression of the signal reduced exploration, indicating a causal role. The findings may inform understanding of addiction, OCD and Parkinson’s disease.
How Disappointment Rewires the Brain: Acetylcholine Helps Mice Break Habits
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Disappointment stings — but it can also be a powerful signal that prompts animals to change course. New research from the Okinawa Institute of Science and Technology (OIST) shows that when mice unexpectedly lose an anticipated reward, a surge of the neurotransmitter acetylcholine in the striatum predicts whether they will abandon the old strategy and try something new.
Study Overview
Researchers trained mice to navigate a virtual maze and rewarded correct choices with a sugary treat. After the animals learned the route and formed an expectation of reward, the scientists altered the path so the treat no longer appeared. While mice navigated the maze, the team used two-photon microscopy to image neurotransmitter release in real time.
Key Findings
When the expected reward disappeared, the striatum showed a pronounced acetylcholine surge. The magnitude of that surge predicted whether a mouse would abandon the learned route and explore alternative paths. Importantly, this cholinergic response appeared only after mice had formed an expectation of reward; it was not simply a reaction to errors during initial training.
To test causality, the researchers suppressed the acetylcholine signal using a viral delivery of a receptor that, when activated, silenced the cholinergic pathway (a chemogenetic approach). With that signal turned off, mice were far less likely to explore new solutions when the task changed, indicating a causal role for acetylcholine in enabling behavioral flexibility.
Implications
These results clarify how disappointed expectation can trigger specific neurotransmitter dynamics that promote adaptive choices. Understanding this mechanism may help researchers develop new approaches for disorders characterized by inflexible behavior, including addiction, obsessive–compulsive disorder, and Parkinson’s disease.
“Our results demonstrated the importance of acetylcholine in breaking habits and enabling new choices to be made,” said co-author Gideon Sarpong, a neuroscientist at OIST.
In short, the brain’s biochemical response to disappointment appears to function as an internal cue to update behavior — nudging animals (and perhaps humans) away from failing strategies toward alternatives that might succeed.
