Sequential reversal learning: a new touchscreen schedule for assessing cognitive flexibility in mice
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ORIGINAL INVESTIGATION
Sequential reversal learning: a new touchscreen schedule for assessing cognitive flexibility in mice Anna U. Odland 1 & Rune Sandahl 1 & Jesper T. Andreasen 1 Received: 4 August 2020 / Accepted: 19 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale The widespread deficits in cognitive flexibility observed across psychiatric disorders call for improved rodent tests to understand the biology of cognitive flexibility and development of better psychotherapeutics. Current reversal learning paradigms have a forced-choice setup that challenges the interpretation of results. Objectives We aimed at developing a free-choice reversal learning test, where images are presented sequentially and animals are free to move, to enable investigation of the cognitive sub-processes that occur during reversal. Methods Behavior in female C57BL/6JOlaHsd mice was characterized using chronic fluoxetine as a reference compound. Additional tests were included to support the interpretation of results and exclude confounding pharmacological effects. Behaviors in vehicle-treated mice were furthermore analyzed for relatedness to deepen the understanding of parameters measured. Results We found that exploitation of the previously rewarded image was independent of exploration and acquisition of the new reward contingency and could be differentially modulated by fluoxetine, supporting recent theories that these processes are not mutually exclusive. Specifically, fluoxetine reduced mistake rate, premature and perseverative responses, and promoted conservative strategies during reversal without affecting hit rate. These effects appeared to be most prominent during the late stage of reversal learning, where accuracy was above chance level. Analysis of behaviors in vehicle-treated mice suggested that exploitation was related to an impulsive-like deficit in response inhibition, while exploration was more related to motivation. Conclusions This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive subprocesses during reversal. Keywords Touchscreen . Cognitive flexibility . Reversal learning . Mouse behavior . Serotonin . Exploitation . Exploration . Extinction . Sequential . Go/no-go
Introduction Highlights • New sequential reversal learning paradigm that separates exploration from exploitation. • Exploitation of previous reward contingencies was independent of exploration of new reward contingencies during reversal. • Exploitation was related to an impulsive-like phenotype, and exploration to motivation. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00213-02005687-6. * Jesper T. Andreasen [email protected] 1
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
Cognitive inflexibility is a transdiagnostic trait that spans a wide range of psychiatric disorders including depression, schizophrenia, substance use, ob
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