Altered corollary discharge signaling in the auditory cortex of a mouse model of schizophrenia predisposition.

Abstract

The ability to distinguish sensations that are self-generated from those caused by external events is disrupted in schizophrenia patients. However, the neural circuit abnormalities underlying this sensory impairment and its relationship to the risk factors for the disease is not well understood. To address this, we examined the processing of self-generated sounds in male Df(16)A+/- mice, which model one of the largest genetic risk factors for schizophrenia, the 22q11.2 microdeletion. We find that auditory cortical neurons in Df(16)A+/- mice fail to attenuate their responses to self-generated sounds, recapitulating deficits seen in schizophrenia patients. Notably, the auditory cortex of Df(16)A+/- mice displayed weaker motor-related signals and received fewer inputs from the motor cortex, suggesting an anatomical basis underlying the sensory deficit. These results provide insights into the mechanisms by which a major genetic risk factor for schizophrenia disrupts the top-down processing of sensory information.