Multimodal mismatch responses in mouse auditory cortex

Our movements result in predictable sensory feedback that is often multimodal. Based on deviations between predictions and actual sensory input, primary sensory areas of cortex have been shown to compute sensorimotor prediction errors. How prediction errors in one sensory modality influence the computation of prediction errors in another modality is still unclear. To investigate multimodal prediction errors in mouse auditory cortex (ACx), we used a virtual environment to experimentally couple running to both self-generated auditory and visual feedback. Using two-photon microscopy, we first characterized responses of layer 2/3 (L2/3) neurons to sounds, visual stimuli, and running onsets and found responses to all three stimuli. Probing responses evoked by audiomotor mismatches, we found that they closely resemble visuomotor mismatch responses in visual cortex (V1). Finally, testing for cross modal influence on audiomotor mismatch responses by coupling both sound amplitude and visual flow speed to the speed of running, we found that audiomotor mismatch responses were amplified when paired with concurrent visuomotor mismatches. Our results demonstrate that multimodal and non-hierarchical interactions shape prediction error responses in cortical L2/3.