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

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.

The dopamine D2 agonist quinpirole impairs frontal mismatch responses to sound frequency deviations in freely moving rats.

AIM: A reduced mismatch negativity (MMN) response is a promising electrophysiological endophenotype of schizophrenia that reflects neurocognitive impairment. Dopamine dysfunction is associated with symptoms of schizophrenia. However, whether the dopamine system is involved in MMN impairment remains controversial. In this study, we investigated the effects of the dopamine D2-like receptor agonist quinpirole on mismatch responses to sound frequency changes in an animal model. METHODS: Event-related potentials were recorded from electrocorticogram electrodes placed on the auditory and frontal cortices of freely moving rats using a frequency oddball paradigm consisting of ascending and equiprobable (ie, many standards) control sequences before and after the subcutaneous administration of quinpirole. To detect mismatch responses, difference waveforms were obtained by subtracting nondeviant control waveforms from deviant waveforms. RESULTS: Here, we show the significant effects of quinpirole on frontal mismatch responses to sound frequency deviations in rats. Quinpirole delayed the frontal N18 and P30 mismatch responses and reduced the frontal N55 MMN-like response, which resulted from the reduction in the N55 amplitude to deviant stimuli. Importantly, the magnitude of the N55 amplitude was negatively correlated with the time of the P30 latency in the difference waveforms. In contrast, quinpirole administration did not clearly affect the temporal mismatch responses recorded from the auditory cortex. CONCLUSION: These results suggest that the disruption of dopamine D2-like receptor signaling by quinpirole reduces frontal MMN to sound frequency deviations and that delays in early mismatch responses are involved in this MMN impairment.

Sound frequency dependence of duration mismatch negativity recorded from awake rats.

AIMS: The brain function that detects deviations in the acoustic environment can be evaluated with mismatch negativity (MMN). MMN to sound duration deviance has recently drawn attention as a biomarker for schizophrenia. Nonhuman animals, including rats, also exhibit MMN-like potentials. Therefore, MMN research in nonhuman animals can help to clarify the neural mechanisms underlying MMN production. However, results from preclinical MMN studies on duration deviance have been conflicting. We investigated the effect of sound frequency on MMN-like potentials to duration deviance in rats. METHODS: Event-related potentials were recorded from an electrode placed on the primary auditory cortex of free-moving rats using an oddball paradigm consisting of 50-ms duration tones (standards) and 150-ms duration tones (deviants) at a 500-ms stimulus onset asynchrony. The sound frequency was set to three conditions: 3, 12, and 50 kHz. RESULTS: MMN-like potentials that depended on the short-term stimulus history of background regularity were only observed in the 12-kHz tone frequency condition. CONCLUSIONS: MMN-like potentials to duration deviance are subject to tone frequency of the oddball paradigm in rats, suggesting that rats have distinct sound duration recognition ability.