Contextual modulation emerges by integrating feedforward and feedback processing in mouse visual cortex.

Sensory systems use context to infer meaning. Accordingly, context profoundly influences neural responses to sensory stimuli. However, a cohesive understanding of the circuit mechanisms governing contextual effects across different stimulus conditions is still lacking. Here we present a unified circuit model of mouse visual cortex that accounts for the main standard forms of contextual modulation. This data-driven and biologically realistic circuit, including three primary inhibitory cell types, sheds light on how bottom-up, top-down, and recurrent inputs are integrated across retinotopic space to generate contextual effects in layer 2/3. We establish causal relationships between neural responses, geometrical features of the inputs, and the connectivity patterns. The model not only reveals how a single canonical cortical circuit differently modulates sensory response depending on context but also generates multiple testable predictions, offering insights that apply to broader neural circuitry.