Bidirectional control of orienting behavior by distinct prefrontal circuits

The prefrontal cortex (PFC) orchestrates voluntary behavior by biasing activity in downstream structures to promote actions consistent with current task goals while inhibiting inconsistent ones. PFC circuits comprise of vastly converging inputs and diverging outputs, but how this anatomical diversity allows it to bidirectionally control specific behaviors remains unclear. Here we use multiple approaches to show that a subdivision of the mouse PFC, the anterior cingulate cortex (ACC), integrates and routes discrete sensory inputs to anatomically segregated populations of projection neurons in order to promote and inhibit goal-directed visual orienting responses. Surprisingly, ACC outputs to the superior colliculus principally inhibit incorrect orienting movements. Optogenetic analyses and a projection-based activity model make the unexpected prediction that feedback from the ACC to the visual cortex is critical for correct orienting, which we confirm. Integrating anatomically non-overlapping but functionally complementary projections for bidirectional control may be a general organizing principle for PFC circuits.