Rapid, automated and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
- Monash University, Australia
Abstract
Anorexia nervosa has among the highest mortality rates of any psychiatric disorder and is characterised by cognitive inflexibility that persists after weight recovery and contributes to the low rates of recovery. What remains unknown is whether cognitive inflexibility predisposes individuals to anorexia nervosa, a question that is difficult to determine from human studies. Our previous work using the most well-established animal model of anorexia nervosa, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA. Here we describe experiments that validate and optimise the first fully-automated and experimenter-free touchscreen cognitive testing system for rats and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model. Firstly, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility measured by this reversal learning task does not predispose rats to pathological weight loss in ABA. Instead, rats that were predisposed to weight loss in ABA exhibited better flexible learning on some aspects of this task prior to ABA exposure. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA exposed (but weight recovered) rats performing much worse than ABA naïve rats on the reversal learning task, an impairment that did not occur to the same extent in rats exposed to food restriction conditions alone. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioural differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes. These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide targets for future studies using the ABA model to investigate potential novel pharmacotherapies for anorexia nervosa.
Data availability
The data generated in this paper can be found at https://doi.org/10.6084/m9.figshare.21539685. A data analysis pipeline for providing the key data per session can be found at https://github.com/Foldi-Lab/PhenoSys-codes. The codes used to create the pose estimation and behavioural segmentation analysis and figures can also be found at https://github.com/Foldi-Lab/PhenoSys-data.
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Raw data for figuresFigShare Dataset doi.org/10.6084/m9.figshare.21539685.v2.
Article and author information
Author details
Funding
Rebecca L. Cooper Medical Research Foundation (PG2019373-Foldi)
- Claire J Foldi
National Health and Medical Research Council (GNT2001722-Foldi)
- Claire J Foldi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were conducted in accordance with the Australian Code for the care and use of animals for scientific purposes and approved by the Monash Animal Resource Platform Ethics Committee (ERM 29143 and 15171).
Copyright
© 2023, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Rapid, automated and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
eLife 12:e84961.
https://doi.org/10.7554/eLife.84961
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