Analysis of deviance detection and adaptation by in vivo calcium imaging of mouse auditory cortex

概要

Detection of subtle but informative cues embedded within the environment requires elaborate sensory processing. The mismatch negativity (MMN) obtained by the human electroencephalogram is considered to reflect deviance detection, and reduced MMN has been reported in schizophrenia patients. The underlying mechanism, however, is unknown and requires elucidation of the responsible circuit in animal experiments. To establish an experimental paradigm of MMN evaluation at cellular resolution in the mouse auditory cortex, I performed in vivo calcium imaging after virus-mediated expression of genetically encoded Ca2+ indicators. Individual fields in the mouse auditory cortex, A1 (primary auditory cortex), AAF (anterior auditory field), and A2 (secondary auditory cortex), were identified by wide-field imaging. I examined deviance detection and adaptation by applying frequency-MMN paradigm, in which stimuli differed only in context while the tonal pitch was identical. I found that AAF and A2 showed larger deviance detection in layer 2/3 excitatory neurons than A1. Furthermore, irrespective of the fields, excitatory neurons in layer 2/3 had larger deviance detection than those in layer 4 or layer 5, whereas adaptation did not differ between layers in all fields. These results suggest that deviance detection is a process with larger involvement of the higher-order auditory cortex, while adaptation may be processed in both the primary and higher-order auditory cortex. The findings in this study support the presence of specific cortical circuits that are responsible for sensitive and reliable detection of meaningful signals embedded in the noisy background. The impairment of these circuits may be involved in the pathophysiology of schizophrenia, a disease known for impaired auditory perception and misattribution of auditory information.