Whether navigating a job interview, meeting someone for the first time, or dealing with an unexpected challenge, success often depends on your ability to adjust your behavior. In some situations, adapting quickly can even be critical to survival.
But how does the brain know when to abandon old strategies and try something new?
New research published in nature communications Let’s shed some light on that question. Neuroscientists at Okinawa Institute of Science and Technology University (OIST) have identified a key brain mechanism that helps animals adapt when conditions suddenly change. The findings could advance our understanding of conditions that make it difficult to break habits, such as addiction, obsessive-compulsive disorder (OCD) and Parkinson’s disease.
“The brain mechanisms behind behavioral changes remain unclear, as adapting to specific scenarios is neurologically very complex. This requires interconnected activity across multiple regions of the brain,” explains co-author Professor Jeffrey Wickens, head of the OIST Neurobiology Research Unit.
“Previous research has shown that cholinergic interneurons, brain cells that release a neurotransmitter called acetylcholine, are involved in achieving behavioral flexibility. Now, using advanced imaging techniques, we were able to see neurotransmitter release in real time and take a closer look at the fundamental mechanisms behind behavioral flexibility.”
How the brain responds to unexpected disappointments
To investigate, researchers trained mice to navigate a virtual maze. The animals learned which routes led to rewards and gradually developed reliable strategies for getting there.
Then scientists changed the rules.
After the reward pathway was switched, the mice unexpectedly failed to receive the expected reward. The researchers used two-photon microscopy to monitor activity in the animals’ brains in response to this surprising result.
“Neurally, we saw a significant increase in acetylcholine release in certain areas of the brain, and behaviorally, more mice exhibited so-called ‘shift-shift’ behavior, where they changed their choice in the maze after missing a reward,” said Dr. Gideon Sarpong, lead author of the study.
“The greater the increase in acetylcholine, the more likely the mice will change their future choices. Our results demonstrated the importance of acetylcholine in breaking habits and enabling new choices.”
Acetylcholine helps break old habits
To test whether acetylcholine was indeed responsible for this behavioral flexibility, the researchers reduced the animals’ ability to produce the neurotransmitter.
The effect was obvious. Mice exhibited much less loss-of-shift behavior and were less likely to adjust their decisions after an unexpected outcome. The results confirmed that acetylcholine plays an important role in helping the brain adapt when conditions change.
Interestingly, not all groups of cholinergic interneurons responded in the same way. Most cells released more acetylcholine, but some small cell clusters showed little change or even decreased activity.
According to the researchers, this could help store information about previously successful actions.
“This shows that mice do not necessarily forget the previous reward pathway, but retain this information in case the situation changes again,” Dr. Sarpong says.
Impact on addiction, OCD, and Parkinson’s disease
The researchers emphasize that behavioral flexibility involves a much larger network than a single neurotransmitter or brain cell type. Multiple brain regions and chemical signaling systems work together to help animals and humans adapt to changing conditions.
Still, the new discovery provides an important piece of the puzzle.
“However, activity in the striatum, where these cholinergic interneurons are maintained, is a central component of this system, so this is an important piece of the puzzle,” Professor Wickens emphasizes.
This research goes beyond advances in basic neuroscience and may ultimately contribute to better treatments for neurological and psychiatric disorders.
“Understanding the function of this neurotransmitter is essential for the treatment of many neuropsychiatric disorders, as acetylcholine levels are often altered in the treatment of neuropsychiatric disorders such as Parkinson’s disease and schizophrenia,” Professor Wickens said.
“Particularly in conditions such as addiction and obsessive-compulsive disorder, we find it difficult to break habits or change behavior. Therefore, understanding the mechanisms of behavioral flexibility may one day help us develop better treatments.”
