An area of the forebrain called the basal ganglia helps people to decide which actions to take—should I eat this apple?—and whether the action had a good (the apple was tasty) or bad (the apple was rotten) outcome. Scientists working with mice have now located a distinct group of neurons within the basal ganglia where these outcomes are evaluated, which could have implications for understanding some of the brain circuitry involved in depression.



Their study, published September 2016 in Nature, was led by Bo Li, Ph.D. of Cold Spring Harbor Laboratory (CSHL), a 2010 NARSAD Young Investigator and 2015 Independent Investigator. Joining Li on the paper were 2013 Young Investigator Sandra Ahrens, Ph.D., and lead author Marcus Stephenson-Jones, Ph.D., a 2014 Young Investigator, who are both postdoctoral researchers at CSHL.

 

Dr. Li and colleagues identify the newly discovered evaluation center as the habenula-projecting globus pallidus, or GPh. “In our functional account of this circuit,” Li said, “we explain how choices are reinforced, based on the results of our actions and how we assess those results.”



Through a variety of experimental techniques, including manipulation of photosensitized neurons with colored laser light, the research team determined that the GPh is essential for evaluating action outcomes, and that this process is controlled by a specific set of inputs from the basal ganglia. In mice that experienced worse-than-expected outcomes, for instance, neurons in the GPh fired more frequently, triggering a response in a connected structure called the lateral habenula. This had the effect of suppressing the activity of dopamine neurons. Inhibition of these neurons corresponds to a “disappointing” evaluation for the action. Conversely, an action that has better-than-expected results sets off a chain of activity through this neural circuit that increases dopamine neural activity—in effect, giving a “thumbs-up” evaluation.



In the future, Dr. Li and colleagues plan to examine this newly-discovered evaluation circuit in mouse models of depression, to determine whether the circuit is altered in any way when depression is produced in the animals.