Periodic Reporting for period 2 - COGBIAS (Neural circuitry and health consequences of cognitive bias)
Periodo di rendicontazione: 2021-02-01 al 2022-01-31
Stress has long been a major concern among researchers interested in health and welfare. Most of their work has considered stress from either a biological or an environmental perspective, focusing on the activation of the physiological systems involved in the stress process or the role of stressful life events in specific diseases. While interesting, if we are to fully understand the effects of stress on health, we must also take into account a psychological perspective that considers an individual’s perception of stress. Indeed, a deep understanding of the neural circuitry underlying psychological stress and its physiological consequences is crucial to meaningfully explain inter-individual variations in vulneraibility to stress. In this framework, COGBIAS firstly aims to characterise the specific neural circuits underlying cognitive bias by which stress is perceived, processed, and transduced into a neuroendocrine response, using zebrafish (Danio rerio) as a model. Secondly, COGBIAS aims to unravel the role of subjective stress on resilience to stress-associated diseases. Hence, the multidisciplinary and unique perspective of this project, combining behavioural, neural, genetic, and physiological sciences, has the potential to reinforce the already European competitiveness in the area of stress-related health and management.
Identifying the cells and circuits that underlie cognitive bias is one of the goal of this project. To achieve it, we have developed strains of transgenic zebrafish in which the expression of a fluorescent protein is controlled by the promoter of specific activity-dependent genes. Specifically, we have created zebrafish that are transgenic for a flourescence protein that is driven by promoters of early-immediate genes. This chemically-controlled visualization system of immediate-early genes it is expected to be extraordinarily useful in identifying brain areas involved in behavioral processes, including cognitive bias. On the other hand, the impact of loss-of-function mutations in the neurokinin (tachykinin (tac)) system on the cognitive appraisal of stressors is being analyzed. Using CRISPR/Cas9 technology, we have created tac3b (tachykinin 3b gene) and tacr3b (tachykinin receptor 3b gene) homozygous knockout zebrafish that will be phenotyped in an optimistic/pessimistic dimension.
Another goal of the project is to assess whether cognitive bias mediates inter-individual variations in susceptibility to stress and stress-related diseases. To achieve it, we have developed two different tasks. In the first task, we have attempted to show evidence that cognitive bias exerts a role in structuring inter-individual differences in the zebrafish gut microbiota under stressful conditions. Our results show stress-mediated alterations in gut microbial composition that are associated with an increase in the abundance of beneficial bacteria for the host. Notably, the stress-mediated alterations in the abundance of specific microbial taxa occur in a phenotype-dependent manner. Furthermore, our functional prediction analyses suggest that judgment bias also drive phenotype-dependent metabolic pathways that are associated to specific microbiome structural compositions. In the second task, we aimed to analyze if cognitive bias is mediating the inter-individual variation in melanoma onset and progression. We tested this hypothesis by using a transgenic zebrafish model for melanoma formation and progression, Tg (mitfa:Hsa.HRAS_G12V,mitfa:GFP)umc1/+. This transgenic line is characterized by an age-dependent formation and apparition of tumour nodules along the zebrafish body, usually in the anal fin. Our results show that in male zebrafish, pessimistic individuals under stress exhibited a higher tumour fraction as compared with pessimistic control fish, which suggest a subtantial role of cognitive bias in modulating melanoma progression under stressful conditions.
So far, these results have been partially presented in two international scientific conferences. On the other hand, aware of the real importance of promoting communication between the scientific community and the general public, several outreach activities have been carried during the course of the outgoing phase. No Website specific has been developed for the project. However, a specific space was created in Oliveira’s group Website with the aim to publicise any important findings of this project (https://oliveiralab.org/people/felipe-espigares/). Furthermore, I’m co-founder and member of SCIENFISH, a Facebook account created to publicise any important findings on fish research, including COGBIAS results. I’m also member and collaborator of SACSIS (http://www.sacsis.es/) an organization that is committed to promoting scientific research and technological innovation at the highest levels. Finally, I participated in the Festival Internacional de Ciência (FIC.A; https://www.fica.pt/) with several activities, including speed dating with scientists and hands-on experiments.
Another goal of the project is to assess whether cognitive bias mediates inter-individual variations in susceptibility to stress and stress-related diseases. To achieve it, we have developed two different tasks. In the first task, we have attempted to show evidence that cognitive bias exerts a role in structuring inter-individual differences in the zebrafish gut microbiota under stressful conditions. Our results show stress-mediated alterations in gut microbial composition that are associated with an increase in the abundance of beneficial bacteria for the host. Notably, the stress-mediated alterations in the abundance of specific microbial taxa occur in a phenotype-dependent manner. Furthermore, our functional prediction analyses suggest that judgment bias also drive phenotype-dependent metabolic pathways that are associated to specific microbiome structural compositions. In the second task, we aimed to analyze if cognitive bias is mediating the inter-individual variation in melanoma onset and progression. We tested this hypothesis by using a transgenic zebrafish model for melanoma formation and progression, Tg (mitfa:Hsa.HRAS_G12V,mitfa:GFP)umc1/+. This transgenic line is characterized by an age-dependent formation and apparition of tumour nodules along the zebrafish body, usually in the anal fin. Our results show that in male zebrafish, pessimistic individuals under stress exhibited a higher tumour fraction as compared with pessimistic control fish, which suggest a subtantial role of cognitive bias in modulating melanoma progression under stressful conditions.
So far, these results have been partially presented in two international scientific conferences. On the other hand, aware of the real importance of promoting communication between the scientific community and the general public, several outreach activities have been carried during the course of the outgoing phase. No Website specific has been developed for the project. However, a specific space was created in Oliveira’s group Website with the aim to publicise any important findings of this project (https://oliveiralab.org/people/felipe-espigares/). Furthermore, I’m co-founder and member of SCIENFISH, a Facebook account created to publicise any important findings on fish research, including COGBIAS results. I’m also member and collaborator of SACSIS (http://www.sacsis.es/) an organization that is committed to promoting scientific research and technological innovation at the highest levels. Finally, I participated in the Festival Internacional de Ciência (FIC.A; https://www.fica.pt/) with several activities, including speed dating with scientists and hands-on experiments.
We have developed a chemically-controlled visualization system in zebrafish of neural activation that it is expected to be extraordinarily useful in identifying brain areas involved in behavioural processes, including cognitive bias. This novel genetic tool for zebrafish, which is based on cutting-edge technology (i.e. Tol2 transposon-mediated transgenesis) is expected to contribute to maintain the European status quo as a region with a high-level of knowledge. Furthermore, our results shed some light on the factors explaining inter-individual susceptibility to stress-related disorders and melanoma progression. These medical problems represent a major economic burden in Europe, and therefore these findings are expected not only be important for academia, but also ultimately for clinical practice, with concrete benefits for the European economy and society in general.