Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia.

Inactivation of medial prefrontal cortex or acute stress impairs odor span in rats.

The capacity of working memory is limited and is altered in brain disorders including schizophrenia. In rodent working memory tasks, capacity is typically not measured (at least not explicitly). One task that does measure working memory capacity is the odor span task (OST) developed by Dudchenko and colleagues. In separate experiments, the effects of medial prefrontal cortex (mPFC) inactivation or acute stress on the OST were assessed in rats. Inactivation of the mPFC profoundly impaired odor span without affecting olfactory sensitivity. Acute stress also significantly reduced odor span. These findings support a potential role of the OST in developing novel therapeutics for disorders characterized by impaired working memory capacity.