Yale Study Revises Understanding of How the Brain Processes and Responds to Rewards

A new Yale study of neuron activity in the brain has revised scientists’ understanding of how the brain processes and responds to rewards.

Researchers have located a set of GABA neurons in the brain’s ventral tegmental area (VTA) that consistently respond to a primary reward. This response differs from the response of dopamine neurons, which previously have been thought to be the principal cells responsible for mediating reward-related behaviors.

Unlike the activity of dopamine neurons, the response in the GABA pathway does not change as animals learn that a cue predicts reward availability, scientists found. Instead, the GABA cells continue to provide a highly stable signal of the size of the primary reward. In reward learning tasks, stimulating this pathway improved the behavior and motivation of animals as they worked to receive rewards across multiple days.

“These findings are exciting because they identify a brain pathway that stably signals the size and intensity of a reward and does not shift during learning, revising our understanding of how reward is encoded in the brain,” said Marina Picciotto, PhD, Charles B.G. Murphy Professor of Psychiatry and professor in the Child Study Center, of neuroscience, and of pharmacology, and the study’s senior author. “This finding also provides a new way to think about how cells in the VTA calculate rewarded outcomes in learning tasks.”

The findings were published in the journal Science Advances. They appear to clarify the role of dopamine and GAPA neurons in the VTA, located in the midbrain.

Dopamine neurons were thought to be principally responsible for mediating reward-related behaviors, however researchers now believe the neurons fire in response to cues that predict reward, and not to the presentation of the reward itself.

In contrast, GABA neurons in the VTA have been thought to primarily be local cells that inhibit dopamine neurons, but the study shows these neurons project out of the VTA to the ventral pallidum, the major output nucleus of the mesolimbic reward system. Importantly, the researchers found that these neurons respond consistently to a primary reward, and that the response of these neurons scales with the size of the reward.

Other Yale researchers involved in the study are Wenliang Zhou, PhD, associate research scientist; Kristen Kim, neuroscience graduate student; and Yann S. Mineur, PhD, research scientist.