bioRxiv Science⌕ Search

Biology subjects

Wilzopolski, J.

Publications and source records attributed to Wilzopolski, J..

4 recordsLinked to original sources

Automatic pain face analysis in mice: Applied to a varied dataset with non-standardized conditions

Biomedical research relies on scientifically validated tools to assess pain, suffering, and distress in laboratory animals to ensure their well-being. In mice, the most frequently used laboratory animals, the Mouse Grimace Scale (MGS) provides a reliable tool for the assessment of facial expression changes caused by impaired well-being. However, no automated tool can yet reliably assess all features of the MGS across different mouse strains under varying experimental or housing conditions in real-time, as the variability present in recorded image datasets poses substantial challenges for computer vision models. Despite this technical difficulty, variability across subsets in terms of mouse strain, treatments, laboratory, and image acquisition setup is essential for paving the way toward MGS assessment under non-standardized conditions in the home cage rather than standardized cage-side recording setups. Against this background, a large and diverse dataset containing five subsets is introduced and a deep learning model was trained to predict the average MGS scores ranging between 0 and 2. It achieved a root mean squared error (RMSE) of 0.26 when trained on all subsets of the dataset, outperforming the average human rater in terms of error magnitude. The correlation between human raters and automated MGS scores was very high (Pearsons r=0.85). In the cross-dataset evaluation, one subset was excluded from training and used for testing the model. This approach yielded higher errors compared to models trained and tested on the same subsets. A model restricted to the feature of orbital tightening showed lower performance than one trained on all facial features of the MGS. Overall, the most reliable model for predicting average MGS scores for a novel dataset is the one trained on the combined subsets. Performance may be further enhanced by fine-tuning the model using human-generated MGS scores for a portion of the novel subset.

animal behavior and cognition↗

Zebrafish facility report on implementation of artificial plants as structural enrichment

There is a broad consensus that husbandry conditions of laboratory animals need constant improvement to guarantee optimal animal welfare and research data quality. Zebrafish (Danio rerio) as one of the main animal models in biomedicine and toxicology are currently kept in barren tanks in most experimental setups, as well as in animal husbandry. Structural enrichment with artificial plants is currently discussed as a potential refinement measure to provide a more diverse environment. It was shown, that this can reduce stress and improve cognitive abilities, survival rate and fertility in these animals. Still, concerns remain regarding its long-term benefits and drawbacks. Therefore, we introduced artificial plants in our husbandry tanks, and evaluated over a one-year period if in our specific system, the benefits would outweigh the risks. Comparing six different lines of zebrafish raised in enriched tanks or under our standard conditions, we saw no significant difference in terms of sex ratio, fertility or pathogen burden. Enrichment increased the survival rate of 4 % during upbringing, albeit not statistically significant due to high variation. When analyzing zebrafish behavior in their 8 L home-tanks, we found less zebrafish in areas close to the plants but rather a preference for the open water in the middle or opposite side of the tank. This effect was even more pronounced at lower holding densities of less than 4 fish per liter. In summary, we found that introducing structural enrichment to our zebrafish facility carried low cost and no detrimental effects for the animals but at the same time benefits were difficult to determine in our readouts as our survival rates already were very high without these measures. We like to encourage other animal facilities to evaluate enrichment measures to ensure a broader discussion on long-term benefits of structural enrichment in zebrafish husbandry systems.

animal behavior and cognition↗

The threshold for intracranial self-stimulation does not increase in rats exposed to chronic unpredictable stress, a systematic review and meta-analysis

The chronic unpredictable stress model is a laboratory rodent model of stress-induced anhedonia. The sucrose preference test, often used to validate it, suffers from being unreliable. Intracranial self-stimulation offers an alternative and is often cited as supporting evidence of the validity of the model. Our aim was to assess whether an increased self-stimulation threshold is found after stress and if such a change correlates with decreases in sweet consumption. We searched PubMed, Embase, and Web of Science for studies in rats exposed to chronic unpredictable stress that employed intracranial self-stimulation. Thresholds, for stressed and control animals, in 23 experiments (11 studies) were pooled. Over 50% of the data was contributed by one research group, so a three-level meta-analytical random effects model was fit to account for methodological differences between different networks of researchers. After this adjustment, we did not find that the self-stimulation thresholds were increased in stressed rats. Pioneering experiments with positive results failed to be replicated by others, although no specific factor could be pointed to as a likely explanation. What is more, the available evidence suggests a lack of connection between sweet preference and self-stimulation, although this relationship has been seldom investigated. Methods known to mitigate biases were frequently absent, as was a transparent report of crucial study details. Our findings challenge the claim made in support of the validity of the model. Further efforts would be well-invested in assessing how reliably other tests of anhedonia have found the effects of the chronic unpredictable stress model.

animal behavior and cognition↗

Development and Application of Home Cage Monitoring in Laboratory Mice and Rats: a Systematic Review

Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside their home cages at selected time points. However, the outcome of such tests can be influenced by the novel environment, the time of day, separation from the social group, or the presence of an experimenter. Moreover, valuable information may be missed when the animals are only monitored in short periods. These issues can be overcome by longitudinal monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state of the art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Both the absolute ([~] x26) and relative ([~] x7) number of HCM-related publications increased from 1974 to 2020. In both mice and rats, there was a clear bias towards males and individually housed animals, but during the past decade (2011-2020), an increasing number of studies used both sexes and group housing. More than 70 % of the studies did not involve a disease model, but the percentage of studies using disease models increased since the 2000s. In most studies, animals were kept for short (up to 4 weeks) length periods in the HCM systems; intermediate length periods (4-12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 hours, while 24-hour measurements have been more frequently since the 2000s. The systematic review demonstrated that manual monitoring is decreasing but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the publication year, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters could be investigated in the home cage in recent times. Over the period covered in this study, techniques for HCM of mice and rats has improved considerably. This development is ongoing and further progress and validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

animal behavior and cognition↗