Updating our Ideas About Dopamine
Post by Anastasia Sares
What's the science?
Dopamine is known as the reward molecule: the chemical that we chase after for pleasure. A more precise theory popular among scientists is that dopamine encodes Reward Prediction Error: its release increases when we fail to accurately guess when the next reward will come, such as a pleasant surprise (ice cream, a hug, a paycheck), and decreases when we experience a lack of these things if we expected them to happen. This week in Current Biology, Kutlu and colleagues challenged this explanation of dopamine, arguing instead that it codes for saliency: responding to signals in our environment that need our attention, whether they are good, bad, or neutral.
How did they do it?
The authors combined a number of methods to measure dopamine activity in the Nucleus Accumbens, one of the major structures involved in motivation and reward. They trained mice using many different combinations of signals (tones or bursts of noise), rewards (sugar-water), or punishments (small foot-shocks or bitter-tasting water). In each experiment, the animals had to learn whether or not to respond to the signals by poking their nose into a small hole. This “nose-poke,” depending on the phase of the experiment, could result in a reward, delay a reward, bring a punishment, or help them avoid punishment. Sometimes the rewards and punishments came without warning, and sometimes the signals happened without any consequence.
The mice themselves were genetically altered (using optogenetics) so that dopamine release could be recorded using a certain wavelength of light. The cells in the Nucleus Accumbens could also be stimulated via another wavelength of light. Tiny fiber-optic cables implanted in the brain were able to deliver and record these light pulses.
What did they find?
The researchers observed dopamine activity for both rewards and punishments, and also when new signals were introduced without any relevance to reward or punishment. The profile of dopamine activity differed slightly between rewards and punishments. For rewards, dopamine activity after the signal could predict behavior on the current trial (whether the mouse poked its nose in the slot). For punishments, it was dopamine activity after the shock that predicted behavior on the next trial.
The researchers tried more things, like varying the intensity of a shock or the concentration of sweet and bitter substances. It turned out that dopamine was responding to intensity as well, and it didn’t matter if it was for a reward or a punishment—the more intense it was, the greater the dopamine response. Punishments without cues and cues without consequences also showed a dopamine response, which diminished with repetition. Adding an irrelevant cue enhanced the dopamine response, even though it had nothing to do with the reward.
Since this pattern of results doesn’t line up with the prevailing theory that dopamine only predicts reward or deviation from reward, the authors made an alternative suggestion: dopamine responds to saliency. In other words, anything that is new, important, and attention-grabbing will generate a dopamine response. Mathematical models using saliency predicted behavior better than the classical model, and stimulating the Nucleus Accumbens made mice act as they would if the signal were more salient, supporting this claim.
What's the impact?
This work calls into question the prevalent idea that dopamine has to do with reward and error prediction. Many neurodegenerative diseases and behavioral addictions involve an imbalance of dopamine, so it is important to accurately understand how dopamine impacts brain function. This will help us evaluate new treatments for these disorders, and also understand human behavior on a deeper level.
Kutlu et al. Dopamine release in the nucleus accumbens core signals perceived saliency. Current Biology (2021). Access the original scientific publication here.