241. NEUROPHYSIOLOGICAL INSIGHTS INTO OMISSION MISMATCH NEGATIVITY: EVIDENCE FROM MACRO CALCIUM IMAGING IN RAT AUDITORY CORTEX

Abstract Background The EEG deficit of mismatch negativity (MMN) is a well-known translational hallmark of schizophrenia. However, the neurophysiological underpinnings of MMN remain to be fully elucidated. Using a calcium brain imaging system, we aimed to visualize the regions responding to a tone-omission oddball paradigm in rats and elucidate the physiological mechanism underlying the EEG response to tone omission as a prediction error. Aims & Objectives Using a calcium brain imaging system, we aimed to visualize the regions for MMN responding to a tone oddball paradigm in rats and elucidate the physiological mechanism underlying MMN as a prediction error. Method We established transgenic rats expressing the GCaMP8 calcium sensor under the Thy1 promoter. The high fluorescence signals from pyramidal neurons allowed us to transcranially monitor the temporal and spatial patterns of neuronal activity across the auditory cortex. The calcium imaging results were then correlated with data from multi-unit recordings in this region. Results In the tone-omission oddball paradigm with intervals shorter than 100 ms, tone omission evoked MMN-related calcium activity in the regions that did not overlap with the areas responding to the standard tone. When the interval was increased to more than 100 ms, the MMN response was diminished. Similarly duration mismatch paradigm also resulted in prediction error responses in approximately the same region. Similar responses were observed in the multi-unit recordings, suggesting the existence of neuronal activities that react to prediction errors in sound sequences. Currently, we are comparing the region and strength of MMN responses in animal models of schizophrenia, established using either the cytokine EGF or the NMDAR blocker MK-801. Discussion & Conclusions Macro-calcium imaging detects MMN responses in the tone-omission oddball as well as in tone duration oddball. The region which is responsible for the detection of these prediction errors is located in the same area of the auditory cortex, but do not overlap with the tonotopy map.