In our day-to-day lives, we’re constantly making a slew of decisions, from immediate matters to prospects on the far horizon. But the evolutionary nuts-and-bolts of how our brains weigh these numerous daily decisions and what role is played by the neurotransmitter serotonin has been shrouded in mystery.

Now, a new study led by an interdisciplinary University of Faculty of Medicine team delivers fascinating findings that potentially unravel a hidden aspect of what our nervous system’s extraordinarily complex serotonin system is really doing inside our skulls.

Published in the journal Nature, this study from a highly impactful international collaboration offers “broad implications across neuroscience, psychology, and psychiatry, enhancing our understanding of serotonin’s role in mood regulation, learning, and motivated behavior.”

The team’s innovative work merges ideas from reinforcement learning (RL) theory—used in neuroscience to better understand learning, behavior, and decision-making—with recent hard-won insights into the filtering properties of the brain’s dorsal raphe nucleus.

An ambiguous pleasure chemical

Serotonin is often painted as the brain’s “pleasure chemical” but its precise role in the nervous system is ambiguous and perplexing: It’s implicated in everything from mood and movement regulation to appetite and sleep-wake cycles. The fact that it’s activated by pain, pleasure and surprise has long been a brain research puzzle.

With this study, the uOttawa-led researchers put forth a unifying perspective on serotonin they dub a “prospective code for value”—a biological code for how the brain places a value for future rewards. This code essentially explains why serotonin neurons are activated in the brain in response to both rewards and punishments, with a preference for surprising rewards.

“Our work asks the question: What does serotonin tell the brain? In a nutshell, we find that its message closely matches the expectation of future rewards,” says senior author Dr. Richard Naud, associate professor at the Department of Cellular and Molecular Medicine and the Department of Physics.

“Your brain needs to compute the expected value of the actions you contemplate and undertake as you interact with a changing world, asking ‘What’s the value of this decision versus that decision in that particular environment?’ That’s a hard problem. So what we think serotonin actually does in the brain is encode the expected value of a particular environment or course of actions in order to ultimately guide everyday decisions,” explains co-author Dr. Jean-Claude Béïque.

The initial spark

The germ of the idea began years ago when first author Emerson Harkin, then a Ph.D. student in Dr. Naud’s lab, started to simulate reinforcement-learning models while working on the biophysical properties of serotonin neurons.

“Nobody seemed to have considered the possibility that serotonin neurons might be activated by changes in the animal’s surroundings, like the start of a signal that reward will arrive soon or the end of a punishment,” says Dr. Harkin, referring to lab experiments with mouse models.

“When we looked at these previous results through the lens of what we had seen under our microscopes and with our electrodes, a lot of results that had previously seemed puzzling or contradictory suddenly started to fit together.”

Next steps

The research team aims to study the role of serotonin on behavior to try and figure out what the rest of the brain does with the neurotransmitter’s messages. Dr. Naud says perhaps finding ways of employing reinforcement-learning theory on frameworks can help them do this.

“The team’s findings show the brain doesn’t work the way machines do. If we perturb the signaling of rewards in the machine, it would do many things that the perturbation in brains don’t do,” he says.