Opposing Influence of Top-down and Bottom-up Input on Excitatory Layer 2/3 Neurons in Mouse Primary Visual Cortex

Processing in cortical circuits is driven by combinations of cortical and subcortical inputs. These inputs are often conceptually categorized as bottom-up, conveying sensory information, and top-down, conveying contextual information. Using intracellular recordings in mouse primary visual cortex, we measured neuronal responses to visual input, locomotion, and visuomotor mismatches. We show that layer 2/3 (L2/3) neurons compute a difference between top-down motor-related input and bottom-up visual flow input. Most L2/3 neurons responded to visuomotor mismatch with either hyperpolarization or depolarization, and the size of this response was correlated with distinct physiological properties. Consistent with a subtraction of bottom-up and top-down input, visual and motor-related inputs had opposing influence on L2/3 neurons. In infragranular neurons, we found no evidence of a difference computation and responses were consistent with positive integration of visuomotor inputs. Our results provide evidence that L2/3 functions as a bidirectional comparator of top-down and bottom-up input.