Dopamine Neurons Drive Cue Response Via Circuit-specific Signals

Dopamine neurons regulate response conditioning through circuit-specific motivational signals to shape cue-controlled behaviors, new research from the University of Minnesota suggests.

University of Minnesota Medical School neuroscientist Benjamin Saunders, Ph.D., used a Pavlovian model of conditioning to see if turning on a light — a simple cue — just before dopamine neurons were activated could motivate action.

The classic Pavlov model combined the ringing of a bell with providing a tasty steak to a dog that, over time, conditioned a dog to drool when the bell rang with or without a steak. In this research, however, there was no “real” reward like food or water, in order to allow researchers to isolate the function of dopamine neuron activity.

“We wanted to know if dopamine neurons are actually directly responsible for assigning a value to these transient environmental cues, like signs,”

said Saunders.

Generation Of Incentive Value

Dopamine neurons, are cells in the brain that become more active when experiencing a reward. They are also the neurons that degenerate in Parkinson’s disease.

“We learned that dopamine neurons are one way our brains give the cues around us meaning. The activity of dopamine neurons alone—even in the absence of food, drugs, or other innately rewarding substances—can imbue cues with value, giving them the ability to motivate actions,”

said Saunders.

Parallel Motivational Roles

To answer the second core question, the researchers targeted specific segments of dopamine neurons—those located in the substantia nigra (SNc) and those located in the ventral tegmental area (VTA). These two types of neurons have historically been studied in different disease research fields — SNc neurons in Parkinson’s disease, and VTA neurons in addiction studies.

The scientists learned that cues predicting activation of the two types of neurons drove very different responses — those predicting the SNc neurons led to a sort of “get up and go” response of invigorated rapid movement. The cue predicting VTA neuron activation, however, became enticing on it own, driving approach to the cue’s location, a sort of “where do I go?” response.

“Our results reveal parallel motivational roles for dopamine neurons in response to cues. In a real world situation, both forms of motivation are critical,” said Saunders. “You have to be motivated to move around and behave, and you have to be motivated to go to the specific location of things you want and need.”

These results provide important understanding of the function of dopamine neurons related to motivations triggered by environmental cues. And this work contributes to the understanding of relapse for those struggling with addictions.

“If a cue—a sign, an alley, a favorite bar, takes on this powerful motivational value, they will be difficult to resist triggers for relapse. We know dopamine is involved, but an essential goal for future studies is to understand how normal, healthy cue-triggered motivation differs from dysfunctional motivation that occurs in humans with addiction and related diseases,”

said Saunders.

The work was supported by grants from the National Institutes of Health and from the Brain and Behavior Research Foundation.

Benjamin T. Saunders, Jocelyn M. Richard, Elyssa B. Margolis & Patricia H. Janak
Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties
Nature Neuroscience volume 21, pages1072–1083 (2018)

Image: RCSB Protein Data Bank, Wellcome Images