How feeling disappointed alters our brains

By Stephen Beech

Feeling disappointed alters our brain chemistry and behavior, reveals new research.

The discovery may give fresh insights into the treatment of diseases and disorders including addiction, obsessive compulsive disorder (OCD) and Parkinson’s disease, say Japanese scientists.

The study of mice by researchers from the Okinawa Institute of Science and Technology (OIST) set out to discover the neural basis of how we switch our behavior when situations change.

Study co-author Professor Jeffery Wickens said: “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.

“Previous work has indicated that cholinergic interneurons - brain cells that release a neurotransmitter called acetylcholine - are involved in enabling behavioral flexibility.

"Here, we were able to use advanced imaging techniques to see neurotransmitter release in real time and delve into the fundamental mechanisms behind behavioral flexibility.”

The researchers trained mice in a virtual maze, teaching them the correct route to receive a reward.

The team then switched the route, leading to an unexpected loss of reward for the mice, and observed the effects of the disappointing change using two-photon microscopy.

Study first author Dr. Gideon Sarpong said: “Neurally, we saw a significant increase in acetylcholine release in certain areas of the brain.

"And behaviorally, we saw more mice displaying what’s known as ‘lose-shift’ behavior - changing their choices in the maze after non-reward.

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“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.”

To confirm their findings, the researchers inhibited acetylcholine production.

They saw a "significant" drop in lose-shift behavior, proving the essential role of the neurotransmitter in behavioral adaptation.

Whilst the majority of cholinergic interneurons produced more acetylcholine, some small regions of cells showed a reduction or no change.

The research team believe it could be a method to preserve previous information on the correct pathways.

Dr. Sarpong said: “This indicates that the mice may not necessarily forget the previous pathway to reward, but retain this information in case the situation changes again."

While the study, published in the journal Nature Communications, presents a leap forward in understanding behavioral flexibility, the team emphasise that the research is just one part of a wider picture.

They explained that other brain regions, cells and neurotransmitters are involved in a complex multi-component system.

Wickens, head of the neurobiology research unit at OIST, said: "It’s an important piece of the puzzle, as the activity of the striatum, where these cholinergic interneurons are held, is a central component of this system.”

The research team hope their findings can improve medicine and healthcare.

Wickens added: “Acetylcholine levels are often altered in treatments for neuropsychiatric disorders like Parkinson’s disease or schizophrenia, so understanding the function of this neurotransmitter is essential in treating many neuropsychiatric disorders.

“In particular, with conditions such as addiction and obsessive-compulsive disorder we see a difficulty in breaking habits and shifting behavior.

"So, understanding the mechanics of behavio gral flexibility may one day help us develop better treatments.”