Dr Laura Lopez-Cruz

Major obstacles to the effective exploration of mood-related processes in neuropsychiatric illness include the lack of animal models that comprehensively recapitulate human presentation, the limited number of assessment tools to evaluate affective state in non-human species and, where such tools do exist, the lack of similarity between them and the methods used in the clinic or in human research. However, recent research has suggested that commonality in a construct referred to as ‘Cognitive Affective Bias’ (CAB) exists between species and behavioural tasks for assessing it have been developed and used as new approach for antidepressant screening in rodents. The basis of CAB concerns the way a subject interprets ambiguous/uncertain stimuli in their environment given their overall affective state. For example, people with anxiety or scoring high in the personality trait neuroticism show pessimistic cognitive bias when presented with ambiguous situations or stimuli (e.g. neutral faces). The identification of population with maladaptive cognitive biases is relevant since have shown to be central to the development and maintenance of depression. On the contrary, optimistic cognitive biases contributes to resilience to depression in humans and correlate with high motivation in both humans and animals. The study of CAB in animals could be used not only as a behavioural platform for antidepressant testing, also to identify individual pessimistic or optimistic-like tendencies, how they correlate with other behaviours and how they are regulated by different neurobiological substrates. The study of individual differences on CABs together with the assessment of other relevant behaviours would also contribute to characterise behavioural phenotypes which may be related with differences on sensitivity to manipulations known by inducing depression-like behaviour. In our lab we developed a touchscreen-based cognitive bias in mice which demonstrated to be sensitive to antidepressant and pro-depressant manipulations and which is currently being forward-translated to humans thanks to the translational potential of touchscreen devises. The present project aims 1) to study individual differences on CAB in mice and explore potential correlations with other relevant behaviours which have shown to correlate with pessimistic or optimistic biases in humans, such us motivation and anxiety, 2) if necessary, to optimise our CAB task to maximise individual differences to stablish a clear “cut off” to classify two types of populations (i.e. ‘optimistic’ vs. ‘pessimistic’ animals) and 3) to study patterns of neuronal activation by cFos in different brain areas known by being involved in the processing of affective information in both populations of mice. The results from this project will contribute to identify the target brain areas for the future analysis of specific mechanisms underlying vulnerability to depression as well as to optimise a touchscreen-based platform for the study of vulnerability to depression with a high translational potential.