Postersession 1
Poster #: 85
Topic: MMN across species
Wednesday, Sep 9, 2015
1st floor

MMN-like and early deviance detection in two animal models of schizophrenia – maternal immune activation and NMDAR antagonism

Patricia Michie1, Lauren Harms2, William Fulham3, Markku Penttonen4, Juanita Todd2, Ulrich Schall5, & Deborah Hodgson2

1Psychology, The University of Newcastle, Callaghan NSW, Australia
2Psychology, University of Newcastle, Callaghan, Australia
3Medicine and Public Health, University of Newcastle, Waratah, Australia
4Psychology, University of Jyväskylä, University of Jyväskylä, Finland
5PRC Translational Neuroscience & Mental Health Research, The University of Newcastle, Callaghan, Australia

Reduction in MMN is a robust finding in schizophrenia thought to reflect glutamate NMDAR hypofunction. We aimed to develop models of schizophrenia-related MMN impairments in rodents exposed to either a neurodevelopmental perturbation of maternal immune activation (MIA), a known risk factor for schizophrenia, or a pharmacological challenge, by administering an NMDAR antagonist (MK-801) known to reduce MMN in healthy individuals.

Pregnant rats were administered the viral mimic, PolyI:C, to induce MIA, or saline, late in gestation. In adulthood, ERPs of male offspring were recorded to two oddball sequences (high- or low-pitch deviant), and a third sequence of randomly-intermixed pitches that controlled for adaptation. Rats were tested on each sequence during three drug-free sessions, followed by three additional sessions after progressively escalating doses of MK-801 (0.1, 0.3, 0.5mg/kg).

Three early components, P13, N18 and P30, and two later broad negative peaks, N55 and N85 were identified. Adaptation-independent deviance-detection was observed in control (saline) rats for high, but not low pitch deviants on both early and late components. MK-801 dose-dependently increased deviance detection on early components, but reduced deviance detection for N55. MIA similarly increased deviance detection on early components, but did not reduce deviance detection on N55.

These findings indicate we have established a rat model of MMN, evident in the late negative peak, N55, which exhibited sensitivity to NMDAR antagonists similar to human MMN. However, we also identified an unexpected increase in deviance detection in early ERP components in response to both MIA and an NMDAR antagonist.