Distinct roles of prefrontal subregion feedback to the primary visual cortex across behavioral states

The mammalian prefrontal cortex (PFC) is thought to modulate cortical sensory processing during behavior through long-range feedback projections. Subregions of the PFC, such as the anterior cingulate cortex (ACA) and ventrolateral orbitofrontal cortex (ORB), exhibit unique patterns of connectivity that may confer distinct roles in feedback modulation of sensory information. Here, we combined axonal tracing, two-photon calcium imaging, and chemogenetic manipulations in mice to determine how projections from the ACA and ORB influence visual processing in the primary visual cortex (VISp). We found that ACA axons conveyed stronger visual-stimulus information than ORB axons, though both conveyed non-visual, behavior-related information. ACA input enhanced visual encoding in VISp neurons and scaled with behavioral arousal, whereas ORB input shaped behavior-related modulation but reduced high-contrast visual encoding. These results reveal distinct feedback roles of ACA and ORB projections, supporting the modular organization of PFC feedback modulation.