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Reactivity to conditioned threat cues is distinct from exploratory drive in the elevated plus maze
Authors:Joe R Hilton  Susannah R Simpson  Emily R Sherman  Will Raby-Smith  Keemia Azvine  Maite Arribas  Jiaqi Zhou  Serena Deiana  Bastian Hengerer  Emma N Cahill
Institution:1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Contribution: Data curation (equal), Formal analysis (lead), Writing - original draft (supporting), Writing - review & editing (supporting);2. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Contribution: Formal analysis (supporting), Writing - review & editing (supporting);3. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Contribution: Formal analysis (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);4. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Contribution: Formal analysis (supporting);5. CNS Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany

Contribution: Writing - original draft (supporting), Writing - review & editing (supporting);6. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Abstract:Fear and anxiety are adaptive states that allow humans and animals alike to respond appropriately to threatening cues in their environment. Commonly used tasks for studying behaviour akin to fear and anxiety in rodent models are Pavlovian threat conditioning and the elevated plus maze (EPM), respectively. In threat conditioning the rodents learn to associate an aversive event with a specific stimulus or context. The learnt association between the two stimuli (the ‘memory’) can then be recalled by re-exposing the subject to the conditioned stimulus. The elevated plus maze is argued to measure the agoraphobic avoidance of the brightly lit open maze arms in crepuscular rodents. These two tasks have been used extensively, yet research into whether they interact is scarce. We investigated whether recall of an aversive memory, across contextual, odour or auditory modalities, would potentiate anxiety-like behaviour in the elevated plus maze. The data did not support that memory recall, even over a series of time points, could influence EPM behaviour. Furthermore, there was no correlation between EPM behaviour and conditioned freezing in independent cohorts tested in the EPM before or after auditory threat conditioning. Further analysis found the production of 22 kHz ultrasonic vocalisations revealed the strongest responders to a conditioned threat cue. These results are of particular importance for consideration when using the EPM and threat conditioning to identify individual differences and the possibility to use the tasks in batteries of tests without cross-task interference.
Keywords:anxiety  elevated plus maze  exploratory behaviour  fear  memory
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