training-laboratory-rabbits-to-refine-routine-husbandry-procedures

Training Laboratory Rabbits to Refine Routine Husbandry Procedures

Non-aversive handling and training techniques for laboratory animals are required to facilitate experimental and routine husbandry procedures, improving ...

operating-biocontainment-procedures-facility-for-laboratory-mice-with

Operating and Biocontainment Procedures of a Facility for Laboratory Mice with a Natural Microbiome: Immunophenotyping Procedure

The use of laboratory mice with a natural microbiome, such as &#34;Wildling mice&#34;, offers a promising research tool for both basic and applied science ...

German Federal Institute for Risk Assessment

German Centre for the Protection of Laboratory Animals (Bf3R)

It has become mandatory for the application for allowance of animal experimentation to rate the severity of the experimental procedures. In order to minimize suffering related to animal experimentation it is therefore crucial to develop appropriate methods for the assessment of animal suffering. Physiological parameters such as hormones or body weight are used to assess stress in laboratory animals. However, such physiological parameters alone are often difficult to interpret and leave a wide scope for interpretation. More recently, behavior, feelings and emotions have come increasingly into the focus of welfare research. Tests like preference tests or cognitive bias tests give insight on how animals evaluate certain situations or objects, how they feel and what their emotional state is. These methods should be combined in order to obtain a comprehensive understanding of the well-being of laboratory animals.

Behavioral Methods for Severity Assessment.

Existing methods for analysis of home cage-based preference tests are either time-consuming, not suitable for group management, expensive, and/or based on proprietary equipment that is not freely available. To correct this, we developed an automated system for group-housed mice based on radio frequency identification: the Mouse Position Surveillance System (MoPSS). The system uses an Arduino microcontroller with compatible components; it is affordable and easy to rebuild for every laboratory because it uses free and open-source software and open-source hardware with the RFID readers as the only proprietary component. The MoPSS was validated using female C57BL/6J mice and manual video comparison. It proved to be accurate even for fast-moving mice (up to 100% accuracy after logical reconstruction), and is already implemented in several studies in our laboratory. Here, we provide the complete construction description as well as the validation data and the results of an example experiment. This tracking system will allow group-based preference testing with individually identified mice to be carried out in a convenient manner. This facilitation of preference tests creates the foundation for better housing conditions from the animals' perspective.

O mouse, where art thou? The Mouse Position Surveillance System (MoPSS)-an RFID-based tracking system.

Laboratory mice are predominantly used for one experiment only, i.e., new mice are ordered or bred for every new experiment. Moreover, most experiments use relatively young mice in the range of late adolescence to early adulthood. As a consequence, little is known about the day-to-day life of adult and aged laboratory mice. Here we present a long-term data set with three consecutive phases conducted with the same male mice over their lifetime in order to shed light on possible long-term effects of repeated cognitive stimulation. One third of the animals was trained by a variety of learning tasks conducted up to an age of 606 days. The mice were housed in four cages with 12 animals per cage; only four mice per cage had to repeatedly solve cognitive tasks for getting access to water using the IntelliCage system. In addition, these learner mice were tested in standard cognitive tests outside their home-cage. The other eight mice served as two control groups living in the same environment but without having to solve tasks for getting access to water. One control group was additionally placed on the test set-ups without having to learn the tasks. Next to the cognitive tasks, we took physiological measures (body mass, resting metabolic rate) and tested for dominance behavior, and attractivity in a female choice experiment. Overall, the mice were under surveillance until they died a natural death, providing a unique data set over the course of virtually their entire lives. Our data showed treatment differences during the first phase of our lifetime data set. Young learner mice showed a higher activity, less growth and resting metabolic rate, and were less attractive for female mice. These effects, however, were not preserved over the long-term. We also did not find differences in dominance or effects on longevity. However, we generated a unique and valuable set of long-term behavioral and physiological data from a single group of male mice and note that our long-term data contribute to a better understanding of the behavioral and physiological processes in male C57Bl/6J mice.

Lifetime Observation of Cognition and Physiological Parameters in Male Mice.

From the preference of one good over another, the strength of the preference cannot automatically be inferred. While money is the common denominator to assess the value of goods in humans, it appears difficult at first glance to put a price tag on the decisions of laboratory animals. Here we used consumer demand tests to measure how much work female mice expend to obtain access to different liquids. The mice could each choose between two liquids, one of which was free. The amount of work required to access the other liquid, by contrast, increased daily. In this way, the value of the liquid can be determined from a mouse's microeconomic perspective. The unique feature is that our test was carried out in a home-cage based setup. The mice lived in a group but could individually access the test-cage, which was connected to the home-cage via a gate. Thereby the mice were able to perform their task undisturbed by group members and on a self-chosen schedule with minimal influence by the experimenter. Our results show that the maximum number of nosepokes depends on the liquids presented. Mice worked incredibly hard for access to water while a bitter-tasting solution was offered for free whereas they made less nosepokes for sweetened liquids while water was offered for free. The results demonstrate that it is possible to perform automated and home-cage based consumer demand tests in order to ask the mice not only what they like best but also how strong their preference is.

Determining the value of preferred goods based on consumer demand in a home-cage based test for mice.

Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans, it may very well describe the lives of many laboratory animals housed in small, barren cages. To make the cages less monotonous, environmental enrichment is often proposed. Although housing in a stimulating environment is still used predominantly as a luxury good and for treatment in preclinical research, enrichment is increasingly recognized to improve animal welfare. To gain insight into how stimulating environments influence the welfare of laboratory rodents, we conducted a systematic review of studies that analyzed the effect of enriched environment on behavioral parameters of animal well-being. Remarkably, a considerable number of these parameters can be associated with symptoms of boredom. Our findings show that a stimulating living environment is essential for the development of natural behavior and animal welfare of laboratory rats and mice alike, regardless of age and sex. Conversely, confinement and under-stimulation has potentially detrimental effects on the mental and physical health of laboratory rodents. We show that boredom in experimental animals is measurable and does not have to be accepted as inevitable.

Bored at home?-A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice.

Current animal protection laws require replacement of animal experiments with alternative methods, whenever such methods are suitable to reach the intended scientific objective. However, searching for alternative methods in the scientific literature is a time-consuming task that requires careful screening of an enormously large number of experimental biomedical publications. The identification of potentially relevant methods, e.g. organ or cell culture models, or computer simulations, can be supported with text mining tools specifically built for this purpose. Such tools are trained (or fine tuned) on relevant data sets labeled by human experts. We developed the GoldHamster corpus, composed of 1,600 PubMed (Medline) articles (titles and abstracts), in which we manually identified the used experimental model according to a set of eight labels, namely: "in vivo", "organs", "primary cells", "immortal cell lines", "invertebrates", "humans", "in silico" and "other" (models). We recruited 13 annotators with expertise in the biomedical domain and assigned each article to two individuals. Four additional rounds of annotation aimed at improving the quality of the annotations with disagreements in the first round. Furthermore, we conducted various machine learning experiments based on supervised learning to evaluate the corpus for our classification task. We obtained more than 7,000 document-level annotations for the above labels. After the first round of annotation, the inter-annotator agreement (kappa coefficient) varied among labels, and ranged from 0.42 (for "others") to 0.82 (for "invertebrates"), with an overall score of 0.62. All disagreements were resolved in the subsequent rounds of annotation. The best-performing machine learning experiment used the PubMedBERT pre-trained model with fine-tuning to our corpus, which gained an overall f-score of 0.83. We obtained a corpus with high agreement for all labels, and our evaluation demonstrated that our corpus is suitable for training reliable predictive models for automatic classification of biomedical literature according to the used experimental models. Our SMAFIRA - "Smart feature-based interactive" - search tool ( https://smafira.bf3r.de ) will employ this classifier for supporting the retrieval of alternative methods to animal experiments. The corpus is available for download ( https://doi.org/10.5281/zenodo.7152295 ), as well as the source code ( https://github.com/mariananeves/goldhamster ) and the model ( https://huggingface.co/SMAFIRA/goldhamster ).

Automatic classification of experimental models in biomedical literature to support searching for alternative methods to animal experiments.

The cognitive bias test is used to measure the emotional state of animals with regard to future expectations. Thus, the test offers a unique possibility to assess animal welfare with regard to housing and testing conditions of laboratory animals. So far, however, performing such a test is time-consuming and requires the presence of an experimenter. Therefore, we developed an automated and home-cage based cognitive bias test based on the IntelliCage system. We present several developmental steps to improve the experimental design leading to a successful measurement of cognitive bias in group-housed female C57BL/6J mice. The automated and home-cage based test design allows to obtain individual data from group-housed mice, to test the mice in their familiar environment, and during their active phase. By connecting the test-cage to the home-cage via a gating system, the mice participated in the test on a self-chosen schedule, indicating high motivation to actively participate in the experiment. We propose that this should have a positive effect on the animals themselves as well as on the data. Unexpectedly, the mice showed an optimistic cognitive bias after enrichment was removed and additional restraining. An optimistic expectation of the future as a consequence of worsening environmental conditions, however, can also be interpreted as an active coping strategy in which a potential profit is sought to be maximized through a higher willingness to take risks.

Development of an IntelliCage-based cognitive bias test for mice.

Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally 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.

A systematic review of the development and application of home cage monitoring in laboratory mice and rats.

Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing (CH) and super-environmental enrichment (SEE).

ArticleTotal : 2	Year
Publication title	2024
Publication title	2024

Article	Year
Behavioral Methods for Severity Assessment. Animals : an open access journal from MDPI\| PubMed ID: 32635341	2020
O mouse, where art thou? The Mouse Position Surveillance System (MoPSS)-an RFID-based tracking system. Behavior research methods\| PubMed ID: 34346041	2022
Lifetime Observation of Cognition and Physiological Parameters in Male Mice. Frontiers in behavioral neuroscience\| PubMed ID: 34539359	2021
Determining the value of preferred goods based on consumer demand in a home-cage based test for mice. Behavior research methods\| PubMed ID: 35469084	2023
Bored at home?-A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice. Frontiers in veterinary science\| PubMed ID: 36061113	2022
Automatic classification of experimental models in biomedical literature to support searching for alternative methods to animal experiments. Journal of biomedical semantics\| PubMed ID: 37658458	2023
Development of an IntelliCage-based cognitive bias test for mice. Open research Europe\| PubMed ID: 37799631	2022
A systematic review of the development and application of home cage monitoring in laboratory mice and rats. BMC biology\| PubMed ID: 37953247	2023
Lockbox enrichment facilitates manipulative and cognitive activities for mice. Open research Europe\| PubMed ID: 39257918	2024

Pia Kahnau

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