How the brain learns from surprises

If our behavior elicits a different response than expected, we learn from it and adapt our behavior in the future. Scientists have now used the mice to study the role that neurotransmitters play in the brain. They showed that the neuromodulator norepinephrine is both involved in the application of learned behaviors and is released when the outcome is different than expected. In this case, norepinephrine provides increased alertness which helps to learn from the event.

The messenger substance norepinephrine acts as a stress hormone and neuromodulator in the body. On the one hand, it is formed in the adrenal medulla, from where it is released to regulate bodily functions such as blood pressure. On the other hand, norepinephrine is produced and released in the brain by what is known as locus coeruleus. This area of ​​the midbrain receives information from many other parts of the brain, which in turn affects them through its own nerve signals and the release of norepinephrine. However, it was still unclear exactly what tasks norepinephrine performed in the brain.

Mouse brain manipulation

A team led by Vincent Breton-Provencher of the Massachusetts Institute of Technology (MIT) in Cambridge was now investigating the function of norepinephrine in the brain of mice. First, scientists placed implants in the brains of animals with which the activity of the bluish site could be monitored and influenced by optogenetic signals. The researchers then put the test animals on water deprivation and taught them to press a lever after hearing a specific beep. If the animals pressed tightly against each other, they were rewarded with a drop of water. On the other hand, with a different, lower signal, the animals could not press the lever. Otherwise, they were punished with an unpleasant puff of air in the face.

During the experiment, scientists changed the volume of high or low tones, respectively. If the prize promising high pitched tone was louder, the mice were more likely to press the lever. On the other hand, with quieter beeps, they seemed more uncertain. The locus coeruleus apparently plays an important role in precisely those situations where the animal is unsure whether it will receive an award. “The animal is pushing because it wants rewards, and the bluish spot gives important signals: push now or the reward will come,” explains Breton-Provencher’s colleague Mriganka Sur. On the other hand, if the scientists inhibited the bluish site with optogenetic signals, the mice were less likely to press the lever when they were unsure. On the other hand, with loud sounds, their behavior remained unchanged.

Norepinephrine for behavioral changes

In addition to the norepinephrine burst at the start of the action, the investigators noticed another burst after the action ended – especially when the outcome was unexpected. When the mouse received an unpleasant gust of air instead of the expected reward, the coeruleus locus released a large amount of norepinephrine, and in subsequent attempts the mouse pressed the lever much less frequently, unless it was sure that it would receive the reward. “The animal constantly adjusts its behavior,” says Sur. “Even after they’ve learned a task, they adjust their behavior based on what they just experienced.”

To rule out that the increase in norepinephrine and the subsequent restriction were solely due to a negative event and not a surprise, the researchers conducted the same experiment with positive surprises, giving the mice a treat at unexpected times. The release of norepinephrine also occurred in this case. Norepinephrine spreads to large parts of the brain, including the prefrontal cortex, which is associated with planning and other higher cognitive functions.

Watch out for surprises

“This work shows that the coeruleus locus encodes unexpected events and that paying attention to these unexpected events is crucial for the brain to evaluate its environment,” says Sur. In future research, scientists want to investigate exactly how the prefrontal cortex responds to signals from the bluish site in order to learn from what they experienced. In addition, they want to study the interactions between norepinephrine and other neuromodulators, such as dopamine, that also respond to unexpected rewards.

Source: Vincent Breton-Provencher (Massachusetts Institute of Technology, Cambridge) et al., Nature, doi: 10.1038 / s41586-022-04782-2

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