Rat call-evoked electrocorticographic responses and intercortical phase synchrony impaired in a cytokine-induced animal model for schizophrenia

Abstract

Patients with schizophrenia exhibit impaired performance in tone-matching or voice discrimination tests. However, there is no animal model recapitulating these pathophysiological traits. Here, we tested the representation of auditory recognition deficits in an animal model of schizophrenia. We established a rat model for schizophrenia using a perinatal challenge of epidermal growth factor (EGF), exposed adult rats to 55 kHz sine tones, rat calls (50-60 kHz), or reversely played calls, analyzed electrocorticography (ECoG) of the auditory and frontal cortices. Grand averages of event-related responses (ERPs) in the auditory cortex showed between-group size differences in the P1 component, whereas the P2 component differed among sound stimulus types. In EGF model rats, gamma band amplitudes were decreased in the auditory cortex and were enhanced in the frontal cortex with sine stimulus. The model rats also exhibited a reduction in rat call-triggered intercortical phase synchrony in the beta range. Risperidone administration restored normal phase synchrony. These findings suggest that perinatal exposure to the cytokine impairs tone/call recognition processes in these neocortices. In conjunction with previous studies using this model, our findings indicate that perturbations in ErbB/EGF signaling during development exert a multiscale impact on auditory functions at the cellular, circuit, and cognitive levels.

Keywords: EGF; Electroencephalogram; Neuregulin-1; Risperidone; Schizophrenia; Sound discrimination.