Omission-evoked auditory mismatch responses in a novel cortical field identified by wide-field calcium imaging in rats

The brain automatically responds to unexpected changes in the environment, and mismatch negativity (MMN) reflects this predictive process. MMN is often reduced in schizophrenia, but its mechanisms remain unclear. To investigate this, we generated transgenic rats expressing GCaMP8 in cortical neurons and performed wide-field calcium imaging of the auditory cortex. Tonotopic mapping showed an overall conserved structure, but A1 and VAF exhibited frequency-dependent changes in gradient direction, forming two fan-shaped maps. As disrupted tonotopy has been reported in schizophrenia, we examined a schizophrenia model. Based on the cytokine hypothesis, we treated rats with epidermal growth factor (EGF) during early postnatal days. Imaging revealed reduced high-frequency responses, enhanced low-frequency responses, and elevated thresholds across the auditory cortex—mimicking schizophrenia. Using an omission-based mismatch response (MMR) paradigm, we found that omitting tones from repeated FM sequences evoked responses in the center of the A1–VAF tonotopic map. Electrophysiological recordings confirmed MMR-related unit activity. Finally, MMR responses were markedly reduced in EGF-treated rats, paralleling deficits observed in schizophrenia. This study identifies auditory cortical regions generating MMR and demonstrates predictive coding deficits in a schizophrenia model rat, providing a platform to explore the neural mechanisms underlying MMN and schizophrenia pathophysiology.