When your brain needs you to pay attention to something
important, one way it can do that is to send out a burst of noradrenaline,
according to a new MIT study.
This neuromodulator, produced by a structure deep in the
brain called the locus coeruleus, can have widespread effects throughout the
brain. In a study of mice, the MIT team found that one key role of
noradrenaline, also known as norepinephrine, is to help the brain learn from
surprising outcomes.
'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 role in signaling surprise, the
researchers also discovered that noradrenaline helps to stimulate behavior that
leads to a reward, particularly in situations where there is uncertainty over
whether a reward will be offered.
Sur is the senior author of the new study, which appears
today in Nature. Vincent Breton-Provencher, a former MIT postdoc who is now an
assistant professor at Laval University, and Gabrielle Drummond, an MIT
graduate student, are the lead authors of the paper.
Modulating behavior
Noradrenaline is one of several neuromodulators that
influence the brain, along with dopamine, serotonin, and acetylcholine. Unlike
neurotransmitters, which enable cell-to-cell communication, neuromodulators are
released over large swathes of the brain, allowing them to exert more general
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 says.
'This suggests they must have very crucial brain-wide functions that are
important for survival and for brain state regulation.'
While scientists have learned much about the role of
dopamine in motivation and reward pursuit, less is known about the other
neuromodulators, including noradrenaline. It has been linked to arousal and
boosting alertness, but too much noradrenaline can lead to anxiety.
Previous studies of the locus coeruleus, the brain's primary
source of noradrenaline, have shown that it receives input from many parts of
the brain and also sends its signals far and wide. In the new study, the MIT
team set out to study its role in a specific type of learning called
reinforcement learning, or learning by trial and error.
For this study, the researchers trained mice to push a lever
when they heard a high-frequency tone, but not when they heard a low-frequency
tone. When the mice responded correctly to the high-frequency tone, they
received water, but if they pushed the lever when they heard a low-frequency
tone, they received an unpleasant puff of air.
The mice also learned to push the lever harder when the
tones were louder. When the volume was lower, they were more uncertain about
whether they should push or not. And, when the researchers inhibited activity
of the locus coeruleus, the mice became much more hesitant to push the lever
when they heard low volume tones, suggesting that noradrenaline promotes taking
a chance on getting a reward in situations where the payoff 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,' Sur says.
The researchers also found that the neurons that generate
this noradrenaline signal appear to send most of their output to the motor
cortex, which offers more evidence that this signal stimulates the animals to
take action.
Signaling surprise
While that initial burst of noradrenaline appears to
stimulate the mice to take action, the researchers also found that a second
burst often occurs after the trial is finished. When the mice received an
expected reward, these bursts were small. However, when the outcome of the
trial was a surprise, the bursts were much larger. For example, when a mouse
received a puff of air instead of the reward it was expecting, the locus
coeruleus sent out a large burst of noradrenaline.
In subsequent trials, that mouse would be much less likely
to push the lever when it was uncertain it would receive a reward. 'The
animal is constantly adjusting its behavior,' Sur says. 'Even though
it has already learned the task, it's adjusting its behavior based on what it
has just done.'
The mice also showed bursts of noradrenaline on trials when
they received an unexpected reward. These bursts appeared to spread
noradrenaline to many parts of the brain, including the prefrontal cortex,
where planning and other higher cognitive functions occur.
'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 says.
The researchers now plan to explore the possible synergy
between noradrenaline and other neuromodulators, especially dopamine, which
also responds to unexpected rewards. They also hope to learn more about how the
prefrontal cortex stores the short-term memory of the input from the locus coeruleus
to help the animals improve their performance in future trials.
The research was funded in part by the Quebec Research
Funds, the Natural Sciences and Engineering Research Council of Canada, a
NARSAD Young Investigator Award from the Brain and Behavior Research
Foundation, the National Institutes of Health, the Simons Foundation Autism
Research Initiative through the Simons Center for the Social Brain, the
National Natural Science Foundation of China, and the NIH BRAIN Initiative.
Resource: Science Daily