Reactivity to conditioned threat cues is distinct from exploratory drive in the elevated plus maze

• Published in: The European journal of neuroscience Vol. 57; no. 1; pp. 54 - 63
• Main Authors: Hilton, Joe R., Simpson, Susannah R., Sherman, Emily R., Raby‐Smith, Will, Azvine, Keemia, Arribas, Maite, Zhou, Jiaqi, Deiana, Serena, Hengerer, Bastian, Cahill, Emma N.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01-01-2023; John Wiley and Sons Inc
• Subjects: Animal models; Animals; Anxiety; Associative learning; Behavioral Neuroscience; Conditioned stimulus; Cues; elevated plus maze; Elevated Plus Maze Test; exploratory behaviour; Fear; Humans; Maze Learning; memory; Research Report; Threats; Tonic immobility; anxiety; elevated plus maze; memory; exploratory behaviour; fear
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15870

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.
Rats were conditioned to react to threats of different modalities (contextual, olfactory and auditory). Ultrasonic vocalisation alarm calls were made by the rats with the strongest memory. Surprisingly, recall of the aversive memory did not impact subsequent exploration of the elevated plus maze.