A study in mice has revealed brain mechanisms behind the way one changes behaviour depending on a situation, findings which could help understand wide-ranging conditions such as addiction and obsessive-compulsive disorder. Researchers from Okinawa Institute of Science and Technology in Japan trained mice to navigate a maze in virtual reality, teaching them the correct route to receive a reward. The route was later switched, resulting in an unexpected loss of reward for the mice. "Neurally, we saw a significant increase in (brain chemical) acetylcholine release in certain areas of the brain (such as striatum). And behaviourally, we saw more mice displaying what's known as 'lose-shift' behaviour -- changing their choices in the maze after (a) non-reward," Gideon Sarpong, first author on the study published in the journal Nature Communications, said.
Acetylcholine is crucial for muscle contraction, learning, memory and attention, with imbalances in the chemical linked to Alzheimer's and Parkinson's diseases, among others. The brain region striatum is known for its role in reward, motivation and forming habits.
"The greater the increase in acetylcholine, the more likely the mice were to change their future choices. Our results demonstrated the importance of acetylcholine in breaking habits and enabling new choices to be made," Sarpong said.
Upon stopping the production of acetylcholine in the mice, the researchers saw a significant drop in lose-shift behaviour, thereby proving the essential role of the neurotransmitter in adapting behaviours.
Co-author Jeffery Wickens, head of the neurobiology research unit at Okinawa Institute of Science and Technology, said previous studies have indicated that cholinergic interneurons -- brain cells that release the chemical acetylcholine -- are involved in allowing behavioural flexibility.
However, "the brain mechanisms behind changing behaviors have remained elusive, because adapting to a given scenario is very neurologically complex. It requires interconnected activity across multiple areas of the brain", Wickens said.
"Rewarded outcomes evoked phasic decreases in acetylcholine, whereas unexpected non-reward following reversal triggered widespread increases that predicted lose-shift behaviour. Targeted inhibition of cholinergic interneurons reduced this adaptive response," the authors wrote.
"These findings suggest that widespread and focal acetylcholine release during unexpected outcomes promotes adaptive response shifts, offering a mechanistic framework for understanding disorders such as addiction and obsessive-compulsive rituals," they said.
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