Assessing Every Child's Potential: Dopamine Serotonin Learning (Part II)

Dr Timothy Kieran O'Mahony, PhD, FRGS

Continues from the last blog ...

Institute for Connecting Neuroscience with Teaching and Learning

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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

“We placed mice in a box and paired different parts of the box with each of those experiences, so mice could vote with their feet which experience they preferred. I will never forget the thrill of walking into the room at the end of the experiment to see all the mice on the side of the box representing both manipulations together.

“It’s very rare in science to get a result so striking that you can see it immediately, and it was our first direct piece of evidence to support the decades-old hypothesis of dopamine-serotonin opponency.”

On the horizon: choreographing dopamine and serotonin to improve psychiatric treatment

The findings suggest that dopamine and serotonin work together, but in opposite ways, to help the brain learn from rewards, the researchers say.

Based on their results, they propose that the two systems act a bit like the accelerator and the brakes on a car. Dopamine encourages reward-seeking behavior by signaling when things are better than expected, creating a ‘go’ signal. In contrast, serotonin seems to put the brakes on this process, creating a ‘stop’ or ‘wait’ signal, potentially helping us to be more patient and consider long-term consequences rather than just immediate rewards.

Effective learning, the study suggests, requires both the ‘go’ signal from dopamine and the ‘wait’ signal from serotonin for an organism to properly evaluate and respond to rewarding opportunities.

The findings also have implications for disorders involving dopamine and serotonin dysfunction, such as addiction, where dopaminergic hypersensitivity and serotonergic deficits contribute to compulsive reward-seeking — and in mood disorders including depression and anxiety, where diminished serotonin signaling might impair behavioral flexibility and long-term planning.

“As dopamine’s role in reward learning has become increasingly clear, the dopamine system has become a natural place to start for studies investigating diseases that involve disrupted reward processing, like addiction and depression,” Cardozo Pinto said.

“Our work showing that the dopamine and serotonin systems form a gas-brake system for reward suggests it will be fruitful for future work to focus on the relative balance between these two systems.”

For example, in addiction treatment, therapies might aim to dampen overactive dopamine signaling while boosting serotonin activity. In depression, the goal might be to enhance both systems to improve motivation and long-term planning. Furthermore, the technical advances the team made to accomplish this study, may have long-standing applications for neuroscience research, Malenka added.

“The novel methodologies we developed for this study can now be applied to a host of fascinating questions related to how the brain mediates adaptive behaviors and what goes wrong in these neuromodulatory systems during prevalent brain disorders such as addiction, depression, and autism spectrum disorders.”

Study authors: Daniel F. Cardozo Pinto, Matthew B. Pomrenze, Michaela Y. Guo, Gavin C. Touponse, Allen P.F. Chen, Neir Eshel, and Robert C. Malenka at Stanford and Brandon S. Bentzley at ​​Magnus Medical in Burlingame, CA.

Funding: National Institutes of Health (NIH) grants (K99DA056573, K08MH123791), a NSF Graduate Research Fellowship, an HHMI Gilliam Fellowship for Advanced Study, a Brain & Behavior Research Foundation Young Investigator Grant, a Burroughs Wellcome Fund Career Award for Medical Scientists, a Simons Foundation Bridge to Independence Award, philanthropic funds donated to the Nancy Pritzker Laboratory at Stanford University, the Berg Scholars program at Stanford School of Medicine, and a Wu Tsai Neurosciences Institute NeuroChoice Initiative Pilot Award.

Competing interests: Eshel is a consultant for Boehringer Ingelheim. Bentzley is a co-founder of Magnus Medical. Malenka is on the scientific advisory boards of MapLight Therapeutics, MindMed, and Aelis Farma.

About this neuroscience and learning research news

Author: Nicholas WeilerSource: StanfordContact: Nicholas Weiler – StanfordImage: The image is credited to Neuroscience News

Original Research: Closed access.“Opponent control of reinforcement by striatal dopamine and serotonin” by Robert Malenka et al. Nature

Abstract

Opponent control of reinforcement by striatal dopamine and serotonin

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) powerfully regulate associative learning. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations.

However, these hypotheses have not been tested directly because it has not been possible to interrogate and manipulate multiple neuromodulatory systems in a single subject.

Here, we establish a mouse model enabling simultaneous genetic access to the brain’s DA and 5HT neurons.

Anterograde tracing revealed the nucleus accumbens (NAc) to be a putative hotspot for the integration of convergent DA and 5HT signals.

Simultaneous recording of DA and 5HT axon activity, together with genetically encoded DA and 5HT sensor recordings, revealed that rewards increase DA signaling and decrease 5HT signaling in the NAc.

Optogenetically dampening DA or 5HT reward responses individually produced modest behavioral deficits in an appetitive conditioning task, while blunting both signals together profoundly disrupted learning and reinforcement.

Optogenetically reproducing DA and 5HT reward responses together was sufficient to drive acquisition of new associations and supported reinforcement more potently than either manipulation alone. Together, these results demonstrate that striatal DA and 5HT signals shape learning by exerting opponent control of reinforcement.

https://neurosciencenews.com/dopamine-serotonin-opposition-learning-28124/

Note: Anterograde Tracing: outlines neurons from their cell bodies to the terminals of their axons; while Retrograde Tracing: outlines neurons in the opposite direction, from the terminals of their axons to their cell bodies. Anterograde and retrograde tracing take advantage of existing transport pathways in neurons.

This is the paper in Nature. Recall that I eliminated all discipline issues in California school last year by doing what they say in this paper:"Optogenetically dampening DA or 5HT reward responses individually produced modest behavioral deficits in an appetitive conditioning task, while blunting both signals together profoundly disrupted learning and reinforcement."

I did it behaviorally since I don't have any way to do it Optogenetically (and kids are not mice)... I used a technique of dampening down the left hemisphere (dopaminergic conditioning to pleasure/reward activation - immediate gratification) and upregulating the right hemisphere (serotoninergic conditioning to reduce impulse and increase long-term thinking with respect to outcomes and consequences).

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(Cardozo Pinto et al., 2024 )

References

Cardozo Pinto, D., Pomrenze, M., Guo, M., Touponse, G., Chen, A., Bentzley, B., Eshel, N., & Malenka, R. (2024 ). Opponent control of reinforcement by striatal dopamine and serotonin. Nature https://doi.org/https://doi.org/10.1038/s41586-024-08412-x