Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice.

Working memory (WM) is the ability to hold on-line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice (which stayed in their homecage) and mice trained in the alternation procedure only (non-adaptive). Following training, a cohort of mice (Experiment A) was tested in the left-right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set-shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non-adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post-synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long-term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non-adaptive groups exhibited increased fEPSP compared to the naïve group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non-adaptive and naïve groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for LTP and dendritic spine density in learning WM tasks.