Sst+ GPi output neurons provide direct feedback to key nodes of the basal ganglia and drive behavioral flexibility.

Abstract

The internal globus pallidus (GPi) is a basal ganglia output nucleus with separate projections to the thalamus and the lateral habenula (LHb). Here, we show a GPi subtype with projections to LHb (GPi-LHb), genetically defined based on glutamate/GABA co-transmission and somatostatin (Sst) expression, also projects back to key nodes in the basal ganglia: the external globus pallidus (GPe), the striatal striosomes, and dopamine neurons in the substantia nigra. We found that the Sst+ GPi population showed strong movement and direction-specific selectivity in a goal-directed choice task, but not during self-paced exploration, and did not signal prediction errors or outcome modulation. During goal-directed behavior, the Sst+ GPi activity slowly evolved with learning of correct choice actions and genetic silencing disrupted the ability to update choice behavior following a task rule reversal. In summary, we have found that Sst+ GPi neurons establish a wide feedback network in the basal ganglia and drive behavioral flexibility.