Brain-wide connectivity patterns of feedforward and feedback cortico-cortical neurons in the mouse secondary visual cortex

Abstract

Feedforward and feedback cortico-cortical neurons are distinct yet spatially intermingled subtypes distributed across cortical layers, playing specialized roles in sensory and cognitive processing. However, whether their presynaptic inputs differ to support these functions remains unknown. Using projection-and layer-specific monosynaptic rabies tracing, we mapped brain-wide long-distance inputs to multiple feedforward and feedback neuron types in VISl (also known as LM), the mouse secondary visual cortex. Overall, long-distance input patterns for these feedforward and feedback neurons were largely similar, as all received the majority of their inputs from VISp, the primary visual cortex, along with substantial inputs from various other cortical and visual thalamic regions. Despite their similarities, these feedforward and feedback types differed in the proportion of long-distance cortical inputs originating from specific visual, retrosplenial, and auditory cortices. These findings reveal the input connectivity patterns of cortico-cortical neurons based on feedforward and feedback projections, providing an anatomical framework for future studies on their functions and circuit integration. KEY POINTS1) Feedforward and feedback cortico-cortical projection neurons in VISl form largely distinct populations that are distributed across multiple cortical layers. 2) Four different feedforward and feedback cortico-cortical projection neuron types receive broadly similar patterns of long-distance input across the brain. 3) Despite overall similarities, feedforward and feedback neurons differ in the relative proportions of inputs from specific areas, including visual, retrosplenial, and auditory cortices.