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Authors & Affiliations
Bastiaan van der Veen, Suellen Almeida-Correa, Lucas Yebra, Serena Deiana, Carsten T. Wotjak, Johann Du Hoffmann
Abstract
Working memory is the ability to hold and handle information for a limited time in order to use previously garnered information. It plays an important role in day-to-day life and is impaired in several neuropsychiatric disorders such as schizophrenia and bipolar disorder. In mice, working memory can be assessed in both, mazes (e.g., water-maze or T-maze) and operant boxes. One of the tasks developed for touchscreen operant boxes is the trial unique non-matched to location (TUNL) task. Although much literature is available showing pharmacological reduction of working memory on this task, the number of studies showing pharmacologically improved performance without a concomitant pharmacological challenge is very limited. The insensitivity of the standard procedure to pro-cognitive treatments may result from ceiling effects and behavioral strategies reached during the extensive training procedure. To enhance sensitivity for pro-cognitive drugs, we adopted a modified procedure [Dexter et al., Frontiers in Neuroscience 2022], which allowed us to modify the complexity and, thus, cognitive load of the task in C57BL/6 mice. Modifications included a sixth response window and intra-session variable cue separation levels. Choice accuracy was dependent on the separation level of the cues. Moreover, performance dropped when introducing a delay. Acute treatment with the GlyT1 inhibitor bitopertin (0.2 mg/kg; s.c.) significantly improved performance during the delay. This demonstrates that the modified TUNL task with its parametric changes such as variable stimulus separation and increased temporal delays creates a window for testing pro-cognitive drugs, forgoing the need of a concomitant pharmacological challenge.