Numerous studies ascertained positive effects of enriched environments on the well-being of laboratory animals including behavioral, physiological and neurochemical parameters. Conversely, such ...conclusions imply impaired animal welfare and health in barren husbandry conditions. Moreover, inappropriate housing of laboratory animals may deteriorate the quality of scientific data. Recommendations for housing laboratory animals stipulate that cages should be enriched to mitigate adverse effects of barren housing. In this context, it is not only unclear what exactly is meant by enrichment, but also how the animals themselves interact with the various items on offer. Focal animal observation of female C57BL/6J mice either housed in conventional (CON) or enriched (ENR) conditions served to analyze the impact of enriching housing on welfare related behavior patterns including stereotypical, maintenance, active social, and inactive behaviors. CON conditions resembled current usual housing of laboratory mice, whereas ENR mice received varying enrichment items including foraging, housing and structural elements, and a running disc. Active and inactive use of these elements was quantitatively assessed. CON mice showed significantly more inactive and stereotypical behavior than ENR mice. ENR mice frequently engaged with all enrichment elements, whereby riddles to obtain food reward and the running disc preferably served for active interactions. Offering a second level resulted in high active and inactive interactions. Structural elements fixed at the cagetop were least attractive for the mice. Overall, the presented data underline the positive welfare benefits of enrichment and that mice clearly differentiate between distinct enrichment types, demonstrating that the perspective of the animals themselves should also be taken into account when specifying laboratory housing conditions. This is particularly important, as the ensuring of animal welfare is an essential prerequisite for reliable, reproducible, and scientifically meaningful results.
Laboratory mice spend most of their lives in cages, not experiments, so improving housing conditions is a first-choice approach to improving their welfare. Despite the increasing popularity of ...enrichment, little is known about the benefits from an animal perspective. For a detailed analysis, we categorized enrichment items according to their prospective use into the categories 'structural', 'housing', and 'foraging'. In homecage-based multiple binary choice tests 12 female C57BL/6J mice chose between enrichment items within the respective categories over a 46-hour period. A new analyzing method combined the binary decisions and ranked the enrichment items within each category by calculating worth values and consensus errors. Although there was no unequivocal ranking that was true in its entire rank order for all individual mice, certain elements (e.g. lattice ball, second plane) were always among the top positions. Overall, a high consensus error in ranking positions reflects strong individual differences in preferences which could not be resolved due to the relatively small sample size. However, individual differences in the preference for enrichment items highlights the importance of a varied enrichment approach, as there does not seem to be one item that satisfies the wants and needs of all individuals to the same degree. An enrichment concept, in which the needs of the animals are central, contributes to a more specific refinement of housing conditions.
Translational biomedical research relies on animal experiments and provides the underlying proof of practice for clinical trials, which places an increased duty of care on translational researchers ...to derive the maximum possible output from every experiment performed. The implementation of open science practices has the potential to initiate a change in research culture that could improve the transparency and quality of translational research in general, as well as increasing the audience and scientific reach of published research. However, open science has become a buzzword in the scientific community that can often miss mark when it comes to practical implementation. In this Essay, we provide a guide to open science practices that can be applied throughout the research process, from study design, through data collection and analysis, to publication and dissemination, to help scientists improve the transparency and quality of their work. As open science practices continue to evolve, we also provide an online toolbox of resources that we will update continually.
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.
Despite tremendous efforts at standardization, the results of scientific studies can vary greatly, especially when considering animal research. It is important to emphasize that consistent different ...personality-like traits emerge and accumulate over time in laboratory mice despite genetic and environmental standardization. To understand to what extent variability can unfold over time, we conducted a long-term study using inbred mice living in an exceptionally complex environment comprising an area of 4.6 m2 spread over five levels. In this semi-naturalistic environment (SNE) the activity and spatial distribution of 20 female C57Bl/6J was recorded by radio-frequency identification (RFID). All individuals were monitored from an age of 11 months to 22 months and their individual pattern of spatial movement in time is described as roaming entropy. Overall, we detected an increase of diversification in roaming behavior over time with stabilizing activity patterns at the individual level. However, spontaneous behavior of the animals as well as physiological parameters did not correlate with cumulative roaming entropy. Moreover, the amount of variability did not exceed the literature data derived from mice living in restricted conventional laboratory conditions. We conclude that even taking quantum leaps towards improving animal welfare does not inevitably mean a setback in terms of data quality.
In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of growth ...factors, promotes brain neurogenesis and improves functional outcome after stroke in young animals. We tested the hypothesis that G-CSF provides a restorative therapeutic benefit in aged animals.
Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 19- to 20-month-old male Sprague-Dawley rats. One hour after reperfusion, the aged rats were treated daily with 15 microg/kg G-CSF and for 15 days total. Rats were behaviorally tested and the brains removed for analysis at 28 days poststroke.
G-CSF treatment after stroke exerted a robust and sustained beneficial effect on survival rate and running function. Transient improvement after G-CSF treatment could be observed for coordinative motor function on the inclined plane test and for working memory in the radial-arm maze test. At the cellular level, G-CSF treatment increased the number of proliferating cells in the subventricular zone and dentate gyrus and also increased the number of newborn neurons in the subventricular zone ipsilateral to the lesion.
These results suggest that G-CSF treatment in aged rats has a survival-enhancing capacity and a beneficial effect on functional outcome, most likely through supportive cellular processes such as neurogenesis.
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.
Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. 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. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time 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 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques 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 year of publication, 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 have been investigated in the home cage more recently.
Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as 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.
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.
The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most ...assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments. Here, we will discuss available protocols for testing learning and memory using the example of the most prevalent animal species in research, the laboratory mouse. A wide range of protocols has been developed in mice to test, e.g., object recognition, spatial learning, procedural memory, sequential problem solving, operant- and fear conditioning, and social recognition. Those assays are carried out with individual subjects in apparatuses such as arenas and mazes, which allow for a high degree of standardization across laboratories and straightforward data interpretation but are not without caveats and limitations. In animal research, there is growing concern about the translatability of study results and animal welfare, leading to novel approaches beyond established protocols. Here, we present some of the more recent developments and more advanced concepts in learning and memory testing, such as multi-step sequential lockboxes, assays involving groups of animals, as well as home cage-based assays supported by automated tracking solutions; and weight their potential and limitations against those of established paradigms. Shifting the focus of learning tests from the classical experimental chamber to settings which are more natural for rodents comes with a new set of challenges for behavioral researchers, but also offers the opportunity to understand memory formation and retrieval in a more conclusive way than has been attainable with conventional test protocols. We predict and embrace an increase in studies relying on methods involving a higher degree of automatization, more naturalistic- and home cage-based experimental setting as well as more integrated learning tasks in the future. We are confident these trends are suited to alleviate the burden on animal subjects and improve study designs in memory research.
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