The Silver Lining in Disappointment

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DA date is boring. But this feeling may be more useful than you think. This appears to help mice change their behavior to avoid similar situations in the future, a skill essential to the survival of many living things.

Scientists at the Okinawa University of Science and Technology (OIST) have discovered that disappointment actually triggers specific changes in the brains of mice that predict adaptive behavior. The results, published in the journal Natural communicationscould help scientists understand a variety of diseases and disorders, from addiction to obsessive-compulsive disorder to Parkinson’s disease.

“The brain mechanisms behind behavioral change have remained elusive, because adapting to a given scenario is very neurologically complex,” co-author Jeffery Wickens, head of the Neurobiology Research Unit at OIST, said in a statement. “It requires interconnected activity in multiple areas of the brain.”

Read more: »Where is my Mind?»

Wickens and his colleagues trained mice to navigate a virtual maze, offering them a sugary reward when the rodents succeeded. They then changed route, so the mice lost the treat. Using an advanced imaging technique known as two-photon microscopy, they monitored the release of neurotransmitters in the mice’s brains in real time as they ran through the maze.

When the gift the mice were expecting suddenly went bad, the scientists observed that acetylcholine flooded the striatum, a part of the brain associated with movement and reward. The greater the neurotransmitter release, the more likely the mice were to change their behavior and try new routes through the maze. This was not the case during the training phase, however, when they made a poor choice, only after learning to expect a sugary treat.

To confirm their findings, the researchers then turned off the source of acetylcholine in the mice – by delivering a specific receptor into their brains using a virus and then activating it – and repeated the experiment. Without the deluge of acetylcholine saturating their brains, the mice were much less likely to look for other ways to solve the maze when the game changed.

“Our results demonstrated the importance of acetylcholine in breaking habits and enabling new choices,” said co-author Gideon Sarpong, a neuroscientist at OIST.

Previous work had already shown that brain cells that release acetylcholine were involved in behavioral flexibility, but it was unclear how exactly this worked. The findings could help scientists better understand the specific roles the neurotransmitter plays in certain neurological disorders.

Perhaps this knowledge might even help ease the bitterness of disappointments, making feelings of defeat a little sweeter.

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Main image: Simple line / Shutterstock

• Kristen French

  Published on December 17, 2025

  Kristen French is an associate editor at Nautilus. She has worked in science journalism since 2013, reporting and writing articles and news for publications such as Wired, Backchannel, The Verge, And New York Review. She holds a master’s degree in science journalism from Columbia University.