Vagiaki, L.-E. | Search bioRxiv

bioRxiv2024

Properties and predictive potential of the pre-ictal oscillatory dynamics in an ex vivo model of epileptiform activity in the different hippocampal subregions

The hippocampus, including the cornu ammonis (CA) and dentate gyrus (DG) subregions, is a brain area highly susceptible to seizure-like activity (SLA). Most studies conducted in vivo have been performed in a single hippocampal subregion. In our study, we used the high [K+] (HK+) model of SLA to investigate the role of oscillatory activity in predicting SLA and in its modulation by anti-epileptic drugs in the three hippocampal subregions (CA1, CA3 and DG). For this, we recorded spontaneous local field potentials (LFPs) in CA1, CA3 and DG subregions from mouse hippocampal slices. We find that the oscillatory activity in the 20 second pre-ictal period is significantly different compared to the oscillatory activity in the absence of SLA or to a more distant period from the ictal event. A classification algorithm revealed that the oscillatory dynamics, particularly in the CA1 subregion, can predict the emergence of an ictal event with high accuracy. Furthermore, oscillatory activity is differentially modulated by anti-epileptic drugs in the different hippocampal subregions. We found that diazepam and carbamazepine modulated the oscillatory activity significantly greater in the CA3 and DG subregions, compared to CA1. Imaging of neuronal activation in the ex vivo model of seizure-like activity, using the Fos protein as an activity marker, revealed a similar subregion-dependent differential modulation following diazepam and carbamazepine perfusion. Therefore, while oscillatory activity in the pre-ictal period in the CA1 subregion can better predict the emergence of ictal events, anti-convulsant drugs have a stronger effect in oscillatory activity in the CA3 and DG subregions.

neuroscience↗

bioRxiv2024

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) naive 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 naive 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.

neuroscience↗