How the brain responds to surprising events

According to a recent MIT research, your brain may pump out a surge of noradrenaline when it requires you to pay attention to something vital.

This neuromodulator, which is generated by the locus coeruleus, a deep brain region, has extensive effects across the brain. The MIT researchers discovered that one important job of noradrenaline, also known as norepinephrine, is to help the brain learn from unexpected events in a mouse study.

"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 MIT's Department of Brain and Cognitive Sciences, a member of MIT's Picower Institute for Learning and Memory, and director of the Simons Center for the Social Brain.

In addition to its involvement in communicating surprise, the researchers revealed that noradrenaline aids in the stimulation of behavior that leads to a reward, especially in instances when a reward is unknown.

Sur is the lead author of a new research published in Nature today. The paper's principal authors are Vincent Breton-Provencher, a former MIT postdoc who is now an assistant professor at Laval University, and Gabrielle Drummond, an MIT graduate student.

Modulating behavior

Along with dopamine, serotonin, and acetylcholine, noradrenaline is one of numerous neuromodulators that affect the brain. Neuromodulators, unlike neurotransmitters, which allow cell-to-cell contact, are released across huge swaths of the brain, allowing them to have broader effects.

"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," Sur explains. "This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation." 

While scientists have learned a lot about dopamine's involvement in motivation and reward seeking, less is known about other neuromodulators, such as noradrenaline. Although it has been related to increased arousal and alertness, too much noradrenaline can cause anxiety.

Previous research has revealed that the locus coeruleus, the brain's principal generator of noradrenaline, takes input from a variety of brain regions and spreads its messages far and wide. The MIT researchers set out to investigate its involvement in a kind of learning known as reinforcement learning, or learning by trial and error, in the new study.

The mice were trained to press a lever when they heard a high-frequency tone but not when they heard a low-frequency tone for this investigation. The mice got water if they responded appropriately to the high-frequency tone, but an unpleasant puff of air if they pressed the lever when they heard a low-frequency tone.

When the tones were louder, the mice learnt to press the lever harder. They were more unsure about whether or not to push when the loudness was lower. The mice became considerably more hesitant to press the lever when they heard low volume tones when the researchers reduced locus coeruleus activity, suggesting that noradrenaline encourages taking a chance on earning a reward in instances when the outcome is unclear.

"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," adds Sur. 

The researchers also discovered that the neurons that produce this noradrenaline signal appear to transfer the majority of their output to the motor cortex, adding to the evidence that this signal motivates animals to act.

Signaling surprise

While the initial burst of noradrenaline appears to motivate the mice to act, the researchers discovered that a second surge happens frequently after the trial is over. These surges were minor when the mice received an expected reward. When the trial's conclusion was unexpected, however, the bursts were substantially greater. The locus coeruleus, for example, released a strong burst of noradrenaline when a mouse received a blast of air instead of the reward it expected.

That mouse would be far less inclined to push the lever in subsequent trials if it wasn't sure it would get a reward. "The animal is constantly adjusting its behavior," Sur explains. "Even though it has already learned the task, it's adjusting its behavior based on what it has just done."

When the mice were given an unexpected treat, they also displayed bursts of noradrenaline. Noradrenaline appeared to diffuse to numerous sections of the brain during these bursts, including the prefrontal cortex, which is where planning and other higher cognitive activities take place.

"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 adds.

The researchers are currently looking at the possibility of a synergy between noradrenaline and other neuromodulators, including dopamine, which responds to unexpected rewards as well. They also seek to learn more about how the prefrontal cortex retains the locus coeruleus's short-term memory in order to assist the animals do better in future trials.