Developmental influences on schizophrenia-like cognitive and neurophysiological outcomes in a rat model of maternal immune challenge

Abstract

The developing brain is sensitive to early-life insults, which can increase the risk of neuropsychiatric disorders such as schizophrenia. Maternal immune system activation during gestation via infection is a known risk factor for schizophrenia. Here we examine the role of early-life immune activation on schizophrenia-related behavioural and electrophysiological outcomes. Pregnant Wistar rats were injected with the viral mimic, Poly(I:C) or vehicle at either gestational day (GD) 10 or GD19. Adult offspring were examined for behaviour (prepulse inhibition (PPI) and working memory) and electrophysiology (generation 50Hz auditory steady-state responses (aSSRs)).Brain tissue was examined for NMDA receptor (NMDAR) binding. Rats exposed to Poly(I:C) at GD10 were found to exhibit reduced PPI, whereas those exposed to Poly(I:C) during late gestation exhibited working memory impairments. In addition, late gestation-exposed rats exhibited reduced power of 50Hz aSSRs, indicating an impaired ability to generate neural oscillations in the high-frequency (gamma) range. Adult offspring exposed to Poly(I:C) on GD19 had increased binding to the NMDAR2A subunit and the NMDAR channel in the hippocampus. Maternal immune activation via a viral mimic was sufficient to alter the trajectory of brain development such that there were long-term impacts of several behavioural and electrophysiological outcomes in adulthood. Several of the behavioural and electrophysiological changes identified here are also found in patients with schizophrenia, indicating that the Maternal Immune Activated rat may model aspects of the disorder.