Effect of electroconvulsive seizures on pattern separation

Abstract

Strategies employing different techniques to inhibit or stimulate neurogenesis have implicated a role for adult-born neurons in the therapeutic effect of antidepressant drugs, as well as a role in memory formation. Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate hippocampal neurogenesis, but it is not known how this relates to either therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the ECS-derived increase in adult-born neurons would manifest in improved pattern separation ability, a memory function that is believed to be both hippocampus-dependent and coupled to neurogenesis. To test this hypothesis, we stimulated neurogenesis in adult rats by treating them with a series of ECS and compared their performances in a trial-unique delayed nonmatching-to-location task (TUNL) to a control group. TUNL performance was analyzed over a 12-week period, during which newly formed neurons differentiate and become functionally integrated in the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the delay between sample and choice, and by varying the spatial similarity between target and distracter location. Although animals learned the task and improved the number of correct responses over time, ECS did not influence spatial pattern separation ability.

Effect of electroconvulsive seizures on cognitive flexibility

“…This difference was observed irrespective of separations, suggesting that there was no difference in pattern separation ability between the two groups. This is in accordance with our previous study on ECS and pattern separation (Svensson et al, ), where we found that performances on minimum, medium, and maximum separations (in the TUNL task) did not differ between ECS‐ and sham‐treated groups. The TUNL and LD tasks tax pattern separation at different stages of the learning and recall process, providing different measures of pattern separation ability.…”

“…4a-c). The choice accuracy and the number of trials and reversals, were generally higher in the maximum separation condition compared with the medium separation condition and lowest in the minimum separation condition, as would be expected since performances on minimum separations place higher demands on hippocampal function (Svensson et al, 2015).…”

“…We have previously investigated if ECS-induced hippocampal neurogenesis improves spatial pattern separation ability in a touch screen-based cognitive test called trial-unique delayed nonmatching-to-location (TUNL, Svensson et al, 2015). In that study, no relation was found between hippocampal neurogenesis and spatial pattern separation ability, as performances of ECS-treated animals did not differ from control animals in the TUNL task.…”

“…On the one hand, some investigations have shown that when neurogenesis is increased, pattern separation ability is enhanced (Creer et al, 2010;Sahay et al, 2011) and when neurogenesis is ablated, pattern separation ability is impaired (Clelland et al, 2009;Tronel et al, 2012). On the other hand, there are studies where no relation between neurogenesis and pattern separation ability could be demonstrated (Groves et al, 2013;Swan et al, 2014;Svensson et al, 2015).…”

Spatial memory impairment in Morris water maze after electroconvulsive seizures

“…Weight was recorded twice; in the beginning and at the end of the experiment. We have in our previous studies used this method to analyse weight gain, and by ‘mixed-design’ we mean that the ANOVA consisted of both within-subject and between-subject factors (29). In statistical follow-up analyses, a linear regression analysis was used to calculate weight gain.…”