Dopamine Serotonin Learning (Part I)

Dr Timothy Kieran O'Mahony, PhD, FRGS

Institute for Connecting Neuroscience with Teaching and Learning

Seattle, WA (206) 499-0176

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Website: https://neuraleducation.org

Author: The Brain-Based Classroom - (Routledge 2021)

Dopamine and Serotonin Work in Opposition for Effective Learning FeaturedNeuroscience

·November 25, 2024

Summary: The interplay between dopamine and serotonin shapes behavior by creating a balance between reward-seeking and impulse control. A novel study demonstrated that both systems work in opposition but are essential for effective learning.

Using optogenetics and innovative tools, researchers found that dopamine acts as an accelerator for rewards, while serotonin serves as a brake, moderating impulsive actions and enabling long-term thinking. This dual control mechanism provides insights into psychiatric conditions like addiction and depression, suggesting potential therapeutic strategies targeting their balance.

Key Facts:

• Dopamine promotes reward-seeking by signaling when things are better than expected, while serotonin moderates these impulses by encouraging patience.

• Effective learning requires both systems to function, as their absence disrupts the ability to link cues to rewards.

• Insights could lead to new treatments for addiction, depression, and other disorders involving dopamine-serotonin imbalance.

Source: Stanford

If you’ve heard of two of the brain’s chemical neurotransmitters, it’s probably dopamine and serotonin. Never mind that glutamate and GABA do most of the work — it’s the thrill of dopamine as the “pleasure chemical” and serotonin as tender mood-stabilizer that attract all the headlines. 

Of course, the headlines mostly get it wrong. Dopamine’s role in shaping behavior goes way beyond simple concepts like “pleasure” or even “reward”. And the fact that it takes weeks or months for serotonin-boosting SSRI antidepressants to work suggests that it’s not actually the immediate jump in serotonin levels that drum out the doldrums of depression, but some still-mysterious shift in downstream brain circuits.

They found that the dopamine and serotonin systems responded in opposite directions — dopamine signaling jumped up in response to the reward, while serotonin signaling fell. Credit: Neuroscience News

A new study from Stanford’s Wu Tsai Neurosciences Institute reveals yet another new facet of these mood-managing molecules.

The research, published on-line November 25, 2024 in Nature, demonstrates for the first time exactly how dopamine and serotonin work together — or more precisely, in opposition — to shape our behavior. 

“In addition to their involvement in our everyday behavior, dopamine and serotonin are implicated in a wide variety of neurological and psychiatric disorders: addiction, autism, depression, schizophrenia, Parkinson’s and more,” said study senior author Robert Malenka, the Pritzker Professor of Psychiatry and Behavioral Sciences at Stanford.

“It’s critical for us to understand their interactions if we are to make progress treating these disorders.”

The theory: dopamine and serotonin are both important for shaping behavior — but how?

Research has long shown that dopamine and serotonin play crucial roles in learning and decision-making across species.

However, the exact interplay between these neurotransmitters has remained unclear. While dopamine is associated with reward prediction and seeking, serotonin seems to moderate these impulses and promote long-term thinking.

Two main theories have emerged: the “synergy hypothesis,” which suggests dopamine handles short-term rewards while serotonin manages long-term benefits, and the “opponency hypothesis,” which proposes the two act as opposing forces balancing our decisions, with dopamine urging immediate action while serotonin counsels patience.

This new Stanford study, part of Wu Tsai Neuro’s NeuroChoice Initiative, provides the first direct experimental test of these competing hypotheses.

The experiment: dual control of dopamine and serotonin during associative learning

Led by graduate student Daniel Cardozo Pinto, the research team created specially engineered mice that allowed them to observe and control both dopamine and serotonin systems in the same animal. 

This innovative approach helped them pinpoint where these two systems interact in the brain — specifically in a limbic region called the nucleus accumbens, which plays a key role in emotion, motivation, and reward processing. 

“This was a very technically demanding project that required us to develop new strategies for recording and manipulating the activity of multiple neuromodulators simultaneously in awake, behaving animals,” Cardozo Pinto shared.

However, he added, “I persevered because I strongly suspected that there would be fascinating interactions between the dopamine and serotonin systems that were being missed by other studies that focused on only one neuromodulator at a time, and it turned out that this was exactly the case.”

Cardozo Pinto and colleagues used their innovative new tools to observe how dopamine and serotonin signals changed in the nucleus accumbens as mice learned to connect a tone and flashing light with a sweet reward.

They found that the dopamine and serotonin systems responded in opposite directions — dopamine signaling jumped up in response to the reward, while serotonin signaling fell. 

The researchers then used optogenetic manipulation (a technique that uses light to control genetically modified neurons) to selectively blunt the normal signaling of each system — either alone or in combination — during reward learning. 

Predictably, given the history of studies linking these signaling systems to reward learning, blocking both dopamine and serotonin signaling made it impossible for mice to link sound and light cues with sugary reward. More surprisingly, restoring either dopamine or serotonin signaling on its own was not enough to allow the animals to learn again. Only with both systems online could animals successfully use the cues to predict the arrival of a reward. 

“The most surprising and memorable moment in the project came when I performed my first optogenetic experiment, where I tested whether mice preferred the experience of a dopamine boost, a serotonin dip, or both together,” Cardozo Pinto recalled.