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Memory bias and affective state: a new cognitive indicator of animal affect

Final Report Summary - MEMORAT (Memory bias and affective state: a new cognitive indicator of animal affect)

Modelling depression in non-human animals (hereafter animals) has been at the heart of many biomedical studies for decades. However, the validity of current animal models of depression is more and more questioned: after decades of use, growing evidence shows discrepancies between the positive outcome of some drugs in these models and their limited efficacy in humans. Moreover, standard animal testing situations model only a few symptoms of human depression. To better assess animal depression, a broader set of psychological, neuroanatomical and cognitive alterations known to occur in depressed patients should be considered. The role of cognition, long recognised as both a potential risk factor and indicator of human affective disorder, has been particularly neglected in animal models and the project focuses on cognitive alterations, particularly in memory functioning. Using rats as our animal subjects, we tested the hypothesis that, just as in depressed humans, animals in an experimentally induced negative affective states retrieve negative information from memory better than positive information, with the opposite being true for rats in a (again experimentally induced) positive affective state.

The first objective of this project aims to develop a task in which the affective valence of the information to be retrieved by rats can be manipulated (e.g. localising food rewards and unpalatable food in an arena). We would have subsequently used the task to test our hypothesis that rats display, just as depressed people, affect-related memory biases. Developing the task has proved challenging, however: a number of rats failed to learn to discriminate the positive / negative locations in the maze, and for those rats showing encouraging sign of discriminative learning, a (too) long duration of training was challenging the ease of application of such a task in the subsequent objectives. We therefore carried, following a similar rationale, a simplified version of this task, involving a lower number of locations to discriminate, and a highly preferred reward for the positive target locations. Similar issues appeared, however (two third of the rats apparently failed to discriminate target from non-target locations, even after several months of training).

We have therefore taken corrective actions related to the methodologies to ensure that the project will not be jeopardised. This includes developing a novel behavioural assay requiring very little training of the animals [therefore tackling issues related to long training durations] to investigate affect-related negative biases in distractibility (sensitivity to distractors), i.e. the tendency to exhibit greater sensitivity to negative than to positive stimuli. Assessing in rats this affect-related cognitive phenomenon also reported in clinically depressed patients, and also particularly neglected in animal models of the human illness, fitted perfectly into the scope of the programme, which aims at investigating phenomenological similarity between stressed animals and depressed people, with the clearly important implications it has for animal models of affective disorder and for animal welfare.

To meet this objective, we assessed sensitivity to positive (preferred, smells of appetitive food) and negative (avoided, brightly illuminated area on the ground) distractors, in a simple behavioural task (travelling across a single-arm maze to return to the home cage) in rats whose affective state was experimentally manipulated (acute restraint stress versus less stressful handling accompanied by food rewards). Drawing our predictions from the phenomenon in humans, we predicted that rats in negative affective state will demonstrate greater distractibility to the negative than to the positive distractor, with the opposite being the case for rats in a comparatively more positive affective state. Current analyses seem to indicate results meet predictions; Dr Fureix is however analysing results from replicate experiments.

Studying animal emotion (affect) is at the forefront of animal welfare science. Cognitive alterations are commonly reported in human affective disorders, and developing novel cognitive approaches to assess animal affect has recently proven to yield substantial developments in the field of animal emotion and welfare. The behavioural assay testing decision-making under ambiguity, initially developed by Scientist in Charge Mendl and colleagues and which has opened up a new research area in animal welfare science (now c.70 published studies in various animal species using this generic approach), is the best example of this. If confirmed, our results will demonstrate further the utility of such an approach, integrating findings from human psychology, cognition and emotion research into animal studies to validate indicators of mental suffering in animals. Moreover, this would provide a simple behavioural assay to assess affect-related cognitive biases, via measuring biases in distractibility (sensitivity to distractors), which, compared to assays testing decision-making under ambiguity, requires little time for the animals to complete the task, sparing the animals from repeated training sessions (3Rs Refinement impact) and the researchers from conducting time-consuming experiments.

Crucially, as being part of the Marie Skłodowska-Curie actions, this project also aimed to equip Dr Fureix with the scientific and transferable skills and experience necessary to make the transition from postdoctoral scientist to a grant holder and manager of her own research group, with a permanent position at a European University. This objective was fully met. Dr Fureix has applied for 6 research funds (of which one is currently evaluated) and has been awarded (in total independence from the scientific in charge) a WALTHAM Collaborative Behaviour & Welfare Award. She has co-supervised to completion one postgraduate research student and two undergraduate students. She has developed strong co-operative networks and working relationships with peers/colleagues locally and nationally (Universities of Bristol, of Lincoln, of Nottingham) and has co-organised the School lunchtime Seminar Series with internal and invited external speakers, which provided a rich foundation to develop further collaborations that will be crucial to becoming world-class researcher. Dr Fureix has attended training and development activities and has practicing further on her communication skills, by giving 3 research seminars and 5 oral conference presentations. Maximising the impact of the scientific results by effectively communicating them to the public was also one of the aims of this fellowship, and Dr Fureix has been involved in a number of public engagement events (see communicating activities). Finally, she has been continuing her commitment to promoting women in science.

By equipping her with the scientific and transferable skills and experience necessary to make the transition from postdoctoral scientist to a grant holder and research group manager, there is no doubt that this Marie Curie fellowship has truly boosted Dr Fureix’s career development as an independent scientist within the European Research Area.