Norepinephrine: How the Brain Responds to Surprising Events

A recent MIT research found that your brain may send a surge of noradrenaline when it requires you to pay attention to something crucial.

The locus coeruleus, a deep brain region, is the source of this neuromodulator, which has broad effects on the whole brain. The MIT researchers discovered that one important function of noradrenaline, commonly known as norepinephrine, is to assist the brain in learning from unexpected results.

“What this work shows is that the locus coeruleus encodes unexpected events, and paying attention to those surprising events is crucial for the brain to take stock of its environment,” says Mriganka Sur, the Newton Professor of Neuroscience in the MIT Department of Brain and Cognitive Sciences, a member of the Picower Institute for Learning and Memory, and the director of the Simons Center for the Social Brain.

Noradrenaline not only plays a function in communicating surprise, but the researchers also found that it aids in promoting behavior that results in a reward, especially in circumstances when a reward is unknown.

The new study's senior author is Sur, and it was released in the journal Nature on June 1, 2022. The paper's primary authors are Gabrielle Drummond, a graduate student at MIT, and Vincent Breton-Provencher, a former postdoc at MIT who is now an assistant professor at Laval University.

Modulating behavior

Along with dopamine, serotonin, and acetylcholine, noradrenaline is one of many neuromodulators that affect the brain. Neuromodulators are released over wide areas of the brain, allowing them to have more widespread effects than neurotransmitters, which allow cell-to-cell contact.

“Neuromodulatory substances are thought to perfuse large areas of the brain and thereby alter the excitatory or inhibitory drive that neurons are receiving in a more point-to-point fashion,” according to Sur. “This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation.”

Less is known about the other neuromodulators, such as noradrenaline, despite the fact that dopamine has been extensively studied for its function in motivation and reward seeking. Noradrenaline has been connected to arousal and enhancing alertness, but too much of it can cause anxiety.

The principal noradrenergic organ of the brain, the locus coeruleus, has previously been demonstrated to accept input from several brain regions and to transmit signals far. The goal of the current study by the MIT team was to investigate its function in reinforcement learning, often known as learning via mistake.

In order to conduct this study, the researchers trained mice to press a lever in response to a high-frequency tone but not a low-frequency tone. When the mice pulled the lever in response to the high-frequency tone properly, they got water; if they did so when they heard the low-frequency tone, they got an unpleasant puff of air.

The mice discovered that louder tones caused them to press the lever more forcefully. They were less convinced whether they should push or not when the loudness was lower. Additionally, the mice were far less likely to press the lever when they heard low volume tones when the researchers blocked locus coeruleus activity, showing that noradrenaline encourages taking a chance on earning a reward in circumstances when the outcome is uncertain.

“The animal is pushing because it wants a reward, and the locus coeruleus provides critical signals to say, push now, because the reward will come,” according to Sur.

More evidence that this signal prompts the animals to behave comes from the discovery by the researchers that the neurons that produce this noradrenaline signal seem to direct the majority of their output toward the motor cortex.

Signaling surprise

The researchers also discovered that a second burst of noradrenaline frequently happens after the trial is over, even if the original burst of noradrenaline appears to motivate the mice to act. These spurts were brief when the mice received an anticipated reward. The spurts were greater, though, when the trial's verdict came as a surprise. For instance, the locus coeruleus released a significant amount of noradrenaline when a mouse got a puff of air instead of the reward it was anticipating.

When it was unknown whether it would earn a reward, that mouse would be considerably less likely to pull the lever in subsequent trials. “The animal is constantly adjusting its behavior,” Sur claims. “Even though it has already learned the task, it’s adjusting its behavior based on what it has just done.” 

On trials where they got an unexpected reward, the mice also had noradrenaline bursts. The prefrontal cortex, which is responsible for higher cognitive tasks like planning, appeared to be affected by these bursts of noradrenaline.

“The surprise-encoding function of the locus coeruleus seem to be much more widespread in the brain, and that may make sense because everything we do is moderated by surprise,” Sur continues.

The next step for the researchers is to investigate any interactions between noradrenaline and other neuromodulators, including dopamine, which also reacts to unanticipated rewards. In order to aid the animals in performing better in next trials, they also seek to understand more about how the prefrontal cortex maintains the short-term memory of the information from the locus coeruleus.