Effects of working memory training on cognitive flexibility, dendritic spine density and long-term potentiation in female mice

Working memory (WM) is a cognitive function that refers to the ability of short-term storage and manipulation of information necessary for the accomplishment of a task. Two brain regions involved in WM are the prefrontal cortex (PFC) and the hippocampus (HPC). Several studies have suggested that training in WM (WMT) can improve performance in other cognitive tasks. However, our understanding of the neurobiological changes induced by WMT is very limited. Previous work from our lab has shown that WMT enhances synaptic and structural plasticity in the PFC and HPC in male mice. In this study, we investigate the effect of WMT on cognitive flexibility and synaptic properties in PFC and HPC in adult female mice. To this end, female adult mice were split into 3 groups: a) naïve which remained in their home cage, b) non-adaptive which learned to alternate the arms in the T-maze but without any delays and c) adaptive which were trained in the delayed alternation task for 9 days. The delayed alternation task was used for WMT. In one cohort, following the delayed alternation task, all mice were tested in the attention set-shifting (AST) task in order to measure cognitive flexibility, and then, the brains were harvested for Golgi-Cox staining to study dendritic spine density. Our results showed that in female mice, there were no differences in performance in the AST among the three groups tested, however, the latency to make a choice was reduced. With regards to dendritic spine density, no significant differences were identified in PFC while increased dendritic spine density was found in the hippocampus of the adaptive group, compared to the naïve group. In a second cohort, acute brain slices were prepared following the delayed alternation task to investigate the synaptic properties in the PFC and the HPC. Evoked field excitatory post-synaptic potential (fEPSP) recordings were performed in either PFC or HPC brain slices. Our results show that tetanic-induced long-term potentiation (LTP) in the PFC was not different among the three training groups. In the HPC, theta-burst induced LTP was significantly increased in the adaptive group also compared to the other two groups. These results reveal both similarities and differences of WMT on cognitive flexibility, dendritic spine density and LTP in females, compared to males.