Opposing influence of top-down and bottom-up input on different types of excitatory layer 2/3 neurons in mouse visual cortex

Processing in cortical circuits is driven by combinations of cortical and subcortical inputs. These signals are often conceptually categorized as bottom-up input, conveying sensory information, and top-down input, conveying contextual information. Using intracellular recordings in mouse 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 these two response types were associated with distinct physiological properties. Consistent with a subtraction of bottom-up and top-down input, visual and motor-related inputs had opposing influence in L2/3 neurons. In infragranular neurons, we found no evidence of a difference-computation and responses were consistent with a positive integration of visuomotor inputs. Our results provide evidence that L2/3 functions as a bidirectional comparator of top-down and bottom-up input.