Khaberni - According to a new study on mice, the underlying behavioral flexibility behind human reactions to disappointment may depend on a single chemical in the brain, the neurotransmitter acetylcholine.
As published on Science Alert citing Nature Communications, these findings could contribute to understanding conditions associated with this neurotransmitter, including addiction, obsessive-compulsive disorder, and schizophrenia.
Important Neurotransmitter
Jeffrey Wichens, a neurobiologist and co-author of the study from the Okinawa Institute of Science and Technology, explains that "levels of acetylcholine often change in treatments for neuropsychiatric disorders such as Parkinson's disease or schizophrenia." Therefore, understanding the function of this neurotransmitter is essential for treating many neuropsychiatric disorders.
Perseverance is a valuable trait, but animals also need flexibility to withstand environmental changes. Survival sometimes depends on the ability to adapt quickly. This flexibility largely depends on external conditions, but it can also reflect internal states such as mood, psychological resilience, and personality.
Wichens states that "particularly in cases like addiction and obsessive-compulsive disorder, there is difficulty in breaking habits and changing behavior."
Thus, understanding the mechanisms of behavioral flexibility could one day help develop better treatments. The new study reveals a mechanism within the brains of mice that seems to help balance perseverance with the occasional need for flexibility.
The experiments explored how unexpected changes in a familiar path that leads to a reward occur in the rodent brain. Wichens says that although previous research has revealed some details about the neural origins of flexible behavior, many key questions remain.
Behavioral Flexibility
Wichens adds that "previous studies have indicated that cholinergic interneurons, which are brain cells that secrete a neurotransmitter called acetylcholine, are involved in enabling behavioral flexibility," explaining that it was possible to "use advanced imaging techniques to monitor the release of neurotransmitters in real-time, and delve into the underlying mechanisms behind behavioral flexibility."
Researchers trained mice to navigate a virtual maze and gave them enough time to learn the reward pathway before suddenly changing it. When the mice attempted to follow the path they had gotten used to, they no longer received the reward they expected.
Using a two-photon microscope and genetically encoded acetylcholine sensor, the researchers monitored brain activity before and after the change, revealing in real time what occurred while the mice were learning the path and again as they processed its sudden interruption.
Neurologically, there was a significant increase in the release of acetylcholine in certain areas of the brain.
Behaviorally, there was an increase in the number of mice exhibiting what is known as "loss and shift" behavior, where they change their choices in the maze after not receiving a reward.
Changing Future Choices
The results suggest that acetylcholine prompts the mice to reconsider their behavior, and "the higher the level of acetylcholine, the more likely the mice are to change their future choices."
To test this explanation, the researchers inhibited the production of acetylcholine in some mice. These mice exhibited more rigid behavior and became less inclined to try new methods, even after the clear failure of their preferred approach.
This supports the idea that acetylcholine helps mammalian brains adapt to unpleasant surprises. However, this neurotransmitter performs multiple functions.
Disappointment
While disappointment in the maze stimulated most of the cholinergic interneurons in the mice to produce more acetylcholine, some groups of cells showed little or no reaction, or even reduced their activity.
Researchers speculate that this might be a mechanism for preserving information about previously successful habits, suggesting that "the mice may not necessarily forget the previous reward pathway, but rather retain this information in anticipation of the situation changing again."
Researchers indicate that behavioral flexibility extends beyond any single neurotransmitter, as it arises from multiple interactions between brain regions and systems. While acetylcholine does not do this alone, "it is a significant part of the picture, as the activity of the striatum, where these cholinergic interneurons are located, is a key element in this system."
Further research will be needed to clarify the role of acetylcholine in all of this, whether to enrich general knowledge of brain functions or to derive revolutionary insights about some neurological disorders.
