How is the cloud helping organizations move and innovate faster? This session will showcase how to modernize IT rapidly by thinking about processes and organizational structures as well as managed cloud services.

The European Directive (2010/63/EU) talks about a ‘climate of care’ (recital 31). Currently, the term mostly used is ‘Culture of care’. Since 2016 there is a Culture of Care network. This network promotes a mindset and behaviour that continuously and proactively works to advance laboratory animal welfare and the 3Rs. The welfare status of an animal is then best represented by the adaptive value of the individual’s interaction with a given environmental setting (Ohl et al., 2012).

Since technology is an integral part of our lives, it would be ignorant to deny a role for technology in enhancing protection of animal welfare and contributing to ‘better science’ at the same time. In the presentation some of the opportunities and challenges are being presented and discussed.

Recent evidences show that common practices in animal facility to meet economics, ergonomic, biosecurity and standardization considerations can be detrimental to animal welfare. We evaluated the DVC system to test different bedding conditions and test what could be more beneficial, in terms of animal locomotion, to animals. Additionally, we tested different housing condition revealing that destructible enrichment (e.g. paper hat) to produce next produced reduction in locomotor activity (e.g. plastic house).

This could be related to thermoregulation as animals in IVC might suffer from cold-stress and the ability (time) to produce proper nesting houses is directly proportional to body temperature of the animals to keep thermoregulation.

Biorhythms of home-cage activity in barrier bred and maintained laboratory mice (C56Bl/6J male and female, NMRI) using DVC
By Karin Pernold, Eric Rullman and Brun Ulfhake
Department of Laboratory medicine, Karolinska Institutet

Using DVC as a non-intrusive technique to monitor in-cage activity 24/7 and a data driven analytical approach, we here present data on biohythmicities covering the circadian, housing routine- triggered rhythms, circannual variations and changes with advancing age.
The study was conducted on a numberof cageskept in the DVC up to a age of 700 days. Using a frequencies and functional data analysis, the key finding of the analyses is that in all cages, regardless of sex and age, the in-cage locomotor activity show consisten circadian, husbandry-triggered and circannual rhythmicities. The overall decline in locomotor activity with age was found to be significant but small up to 16 months of age after which it became more marked.

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Background and aim

Aging is an inevitable phenomenon that has been defined in different ways. Caloric restriction is so far the only know method to reduce or postpone the “aging effects” and to prolong lifespan. Previous studies on mice and caloric restriction has indicated that mice on dietary restriction are more active in behavior tests and has a healther appearance in higher age compared to ad libitum fed controls. Here we have used DVC technology to investigate if the undisturbed, home-cage activity patterns are different between the two diet regimes as well as if it changes with increasing age.

Materials and methods

We used three cohorts of C57BL/6J mice, males and females, and recorded in-cage activity using DVC technology starting from age 2-16 months. Both females and males were subjected to a moderate dietary restriction (DR) to approximately 70% caloric intake compared to what the ad libitum fed control groups eat. The food to the DR groups was weighed and distributed once daily in the morning, at least 4 hours after lights went on in the holding room.

Results and conclusion

We could detect a small, but yet statistically significant decrease in activity levels in the home cage in all three ad libitum fed cohorts. When comparing specific responses to external stimuli, such as the increased activity around time for lights on and the two activity peaks during lights off period, we found that the intensity of these responses decreased during aging. In the the two groups on DR (males and females) we identified a complete change in activity patterns just after diet regime had been introduced. The highest activity levels were focused to a few hours around time for feeding at mid day and the remaining time displayed low activity. The overall daily activity levels was however not different between the DR groups and the ad libitum fed control groups.

Nurturing the combination of animal welfare principles, reproducibility and scientific excellence in the field of rodent model research remains challenging and requires constant innovation and advancement in methods, equipment and data analysis. To facilitate cutting edge biomedical research, with the highest data density, collected from the fewest animals and with utmost care for minimizing sources of error to deliver required statistical power, is the brand promise of Promethion CORE rodent phenotyping platforms. Having said that, with the 3R’s implemented in practice in our design philosophy, we advocate for the inclusion of the 4th R – reproducibility.

With the quality and density of data stored in a raw form, collected transparently from animals housed in low stress equipment, we can deliver on the elusive goal of increased reproducibility, but also assure higher translatability of model data in biomedical, pharmaceutical and longevity research. Finally, being able to pose post-hoc questions and validate hypothesis based on raw data alone, without the need to utilize animals, following the original experiment, further aids in the commitment to the culture of animal care.

Conclusions:

• Low stress equipment design eliminates the need for extensive acclimation in rodent experimentation, assuring animal well-being but also increasing throughput (study number per unit of time) and quality of data collected.
• Transparent, dense and reproducible data, collected using highest resolution and accuracy analyzers assures compliance with the Reduce, Refine and Reproduce policies of the “4Rs”.
• Thanks to a system designed by scientist for scientists the data collected can produce answers to questions long after the original hypothesis has been formulated and the experiments performed.

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The Animal Sciences and Technologies unit in AstraZeneca were interested in evaluating the applications of the automated recording of laboratory animal movement provided by the Tecniplast Digital Ventilated Cages (DVC®) rack. In this study we have investigated those applications in the context of a standard oncology study regularly run in the animal unit to evaluate the anti-tumoral efficacy of new drugs.

Firstly, we evaluated the possible effects of housing the mice on DVC® racks on tumour growth and response to treatment. Secondly, we analysed the effect of disease progression on the diurnal cycle and movement of female BALB/C. And finally, we investigated how animal behaviour is influenced by human interaction and bedding change. Our results show that housing the animals in DVC® rack does not alter either the tumour growth or the response to treatment compared to housing in standard green line caging. When analysing the movement data obtained by the DVC® rack, we observed that tumour volume had a significant impact in animal movement, potentially making movement an equivalent measure of disease progression/regression as tumour volume.

Finally, we observed that both cage bedding change and human interaction influenced the average movement by increasing or decreasing it, respectively. This study has proven that housing laboratory mice in DVC® racking is equivalent to standard green line caging. Moreover, the data obtained from the automated recording of movement suggests that this has the potential to be used as a predictor of disease progression and regression, and to evaluate the effect of human interaction on animal behaviour.

We now plan to evaluate additional applications of this feature in the context of other diseases, and to refine our methods of animal handling.

Background:

In Vitry’s rodent vivarium, we have previously tested the digital ventilated cage rack (DVC, Tecniplast) to improve our cleaning procedures using magnetic impedance to monitor litter moisture. The driver of our most recent project was to use this same technology to record locomotor activity in the home cage where animals are housed in group, therefore without any disturbance of their spontaneous usual behavior. This is an innovative and efficient approach as compared to standard methods for which animals are transferred for punctual assessment to a dedicated lab environment and often isolated, generating stress and impacting data interpretation.

The problem:

To better detect adverse or anticipated effects in animals (to be applicable to welfare or scientific concerns), we want to monitor locomotor activity 24/7 (including during the most active nocturnal period) in group housed mice without disturbing their standard home cages. We also want the data acquisition to be combined with an analysis process efficient and simple enough to provide the results every single morning (i.e. in nearly real time), so that researchers, technicians and veterinarians can take decisions without any delay. The test: Using the DVC, we tested the effects of reference compounds, such as cyclophosphamide and cisplatine, and were able to detect the decrease n locomotor activity from the very first night after administration. The sensitivity was evaluated by treating one animal housed in a group of 3, 4 or 5 and we could demonstrate that the best conditions to detect adverse effects with the DVC would be to limit groups to 4 animals per cage. These promising results will be used to adjust our internal procedures to the most appropriate sensitivity and predictivity conditions.

Outcome:

The DVC appears as a transformative solution, bringing data recording and analysis directly in the vivarium as opposed to historical methods working the other way around. The first recordings and results show promising results in the pilot implementations. Pending additional solutions to include video analysis and help in identifying individual animals, the DVC provides relevant results (less impact and influence of stress induced changes) and helps promoting and improving animal welfare (less stress linked to modifications of housing conditions).

DSI has been continuously pioneering the field of in-vivo physiological monitoring since the last 30+ years. Providing new collaborations with key manufacturer in the life sciences market (e.g. Noldus, Sable and Tecniplast), DSI has generated new solutions to serve the ever-evolving market that requests more for the animals in terms of data but also always in the respect of animal welfare (3Rs). Example of such collaborations will be provided and vision of where DSI is moving in the future.

Reproducibility in preclinical research is critical benchmark of the quality of our science. Achieving it requires specific attention to management of data quality and data transparency processes. Research and press coverage of this topic reveal frequent and systemic sources of error in the identification of inputs to research, including cell lines, reagents, mouse genotypes and even the individual identities of the subjects of research, the rodents themselves. Misidentification errors are also compounded by data transcription errors, lack of data assurance and even deliberate data falsification. The true cost to our industry of poor quality data in our research and the inefficient management of data capture, storage, retrieval and analysis is staggering. This presentation offers an insight into the challenges that need to be addressed and, importantly, a simple, cost effective solution. The Missing Link is Digital Identification. This presentation explains what it is and how, with supporting digitally ready systems, the data quality issues that undermine Reproducibility in preclinical research can be addressed

Successful adoption of novel technologies at large-scale is often determined by the complexity of their learning curves. This is also paired with the ability of proponents to make users fully exploiting all the potentials these new technologies can offer to them. No differences are seen in home cage monitoring which, on the one hand is a breakthrough in the way data are non-intrusively collected directly from the home cage, on the other hand requires careful experimental design, data analysis and statistics to fully benefit from the vast and rich amount of data at hand.

This talk sheds light on some key aspects in the design of experiments with home cage monitoring systems, focusing on raising user awareness on how to properly use these technologies to fully benefit from the collected data. There is no surprise that powerful technologies require proper control which, tailored to home cage monitoring, translates into careful experimental design, proper set up of environmental conditions, appropriate data analysis and finally, by drawing conclusion with proper statistical testing.

A large spectrum of ‘classical’ behavior assays exists to assess emotional and cognitive function of mice from anxiety to fear and from innate to learned. However, these assays have (1) commonly short test duration, (2) require experimenter-based interference (coercion: transfer, handling, novelty) as unspecific stressors, and (3) are commonly performed consecutively along the light (inactivity) or sometimes the dark (activity) phase of mice. Hence, significant performance differences in have been reported depending on the time of testing in the circadian phase. Therefore, a home cage-based passive avoidance (hcPA) system was developed for individually housed male mice. Mice were habituated to their home compartment with a computercontrolled door providing access to the adjacent test compartment [1] with experiments monitored over one week. These experiments yielded the following results:

(1) Substrain differences exist between C57BL/6J and 6N mice in circadian activity.

(2) There were considerably longer latencies (T1/2 = 1.8 hour) to re-enter the test compartment in hcPA than commonly offered in ‘classical’ PA (tonic fear) followed by fast extinction of fear.

(3) C57BL/6N exhibited longer retention latencies than C57BL/6J mice in hcPA than in ‘classical’ PA [2], but no delayed extinction compared to C57BL/6J mice [3].

(4) Despite removal of unspecific stressor inter-individual variation was high (epigenetic contribution).

(5) Some individuals did not re-enter the test compartment within 48 hours (PTSD-like phenotype?).

(6) Test compartment entries occurred predominantly in the dark phase (thus correlate with general activity).

(7) Stretch-attend posture (body length) served as unambiguous index of risk assessment in the door area.

(8) Increased reinforcement (3x and 5x shock exposure) resulted in retention latency drop conform the expectation of performance impairment for complex tasks based on the Yerkes-Dodson law [4].

(9) Delayed shock exposure (>7.5 min after test compartment entry) during training resulted in retention latency decrease (hcPA impairment = latent inhibition [5]).

(10) DBA/2J mice, which are more susceptible to negative reward [6], showed PA but not hcPA impairment.

(11) Enrichment of mice before hcPA experiments resulted in faster habituation to the home compartment but had no effect on hcPA performance.

Based on these results it is obvious that refinement of experimental conditions avoids unspecific stressors when experiments come to the animals (and not vice versa). It is highly recommended to adjust the experimental conditions to the ecological/ethological needs of the animals and not to the needs of the researcher and/or biotechnician. It is important to exploit unambiguous behavioral measures (DSM-V symptoms: avoidance) and acknowledge important mouse substrain differences [7]. Our results frequently yielded opposite outcomes compared to results from classical behavior assays thereby challenging the acceptance of classical assays as experimental ‘gold standard’.

Only by combining animal welfare with scientific improvements can we seriously address the reproducibility and replicability issues and the translational relevance of rodent phenotyping in behavioral neuroscience [8]. This all depends on the integration of new technological developments and sophisticated but absolutely transparent data analyses.

References: [1] Hager et al. (2014) Front Behav Neurosci 8:314. [2] Baarendse et al. (2008) Hippocampus 18, 11-19. [3] Stiedl et al. (1999) Behav Brain Res 104, 1-12. [4] Diamond et al. (2007) Neural Plast 2007, art. ID 60803. [5] Lubow & De La Casa (2005) Psychon Bull Rev 12, 806-821. [6] Youn et al. (2013) Behav Brain Res 226, 397-403. [7] Åhlgren & Voikar (2019) Lab Anim 48, 171-180. [8] Kafkafi et al. (2018) Neurosci Biobehav Rev 87, 218-232.

The Laboratory of Integrative Systems Physiology, headed by Professor Johan Auwerx, has been using a systems genetics paradigm to gain a better understanding complex trait relating to metabolism and aging. The newest of these efforts is the Hybrid Diversity Panel healthspan and disease interception study. This panel comprises 90 mouse strains (30 BXD, 30 CC, and 30 inbred) that will be subjected to longitudinal tissue collection and phenotyping pipelines.

The project will allow to simultaneously study, at a population level, the effect of natural aging on cardiometabolic and neurobehavioral clinical traits, coupled to deep tissue molecular traits (transcriptomics, proteomics, metabolomics, lipidomics). Using systems genetics analyses, novel healthspan modulators could be identified, followed by appropriate in-silico or in-vivo validation in multiple organisms including humans. The DVC constitutes an integral part of the phenotyping pipeline and allows to measure the activity patterns of all these animals in their homecage, a unique opportunity to assess the effect of genetics on baseline activity and behavior, and consequently, the relationship between this activity and other clinical and molecular traits.

Preliminary data from one timepoint suggest that each strain has a distinctive and robust “footprint” in terms of total activity, light-dark cycling, as well as spatial preferences. Additional data from the same strains at different ages will shed light on how activity patterns evolve with age in a genotype-dependent manner and may serve as a reference database for mouse activity.

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Environmental enrichment is an important component of an animal care program. It accommodates the innate behavioral needs of laboratory animals and enhances their welfare by giving them stress resilience to experimental manipulation and life in the vivarium. Behavioral, physiological and biological parameters are often used to evaluate the benefit of a new enrichment but little information is available on how different enrichment strategies might impact group pattern of activity and response to common husbandry procedures. Increased homecage activity has been correlated with increased aggression in males and longer bouts of activity during a period normally utilized for rest may lead to circadian disruption and have negative implications for welfare.

Here, we measured physiological parameters and in-cage activity of group housed male and female C57BL/6Crl mice held in a standard and complex environmental enrichment for 42 days and assessed their response to recurrent interventions such as bedding change and animal visual inspection. Mice with standard enrichment received a red polycarbonate shelter and two cotton squares while mice in complex enrichment had a red polycarbonate mezzanine featuring two side ladders to increase floor space and visibility, as well as, crinkled paper for nest building. Bedding change caused an alteration of the nocturnal activity pattern in all groups with animals held in standard enrichment showing longer diurnal response to the procedure. Females in standard enrichment revealed higher activity and longer duration of the response to visual inspection while males in complex enrichment demonstrated fewer bout events and fight wounds.

Lastly, comparison of gender revealed males displayed less motility and lower duration of the response to procedures than females in both housing conditions. Together our results suggest that environmental enrichment might influence the animal’s ability to cope with potential stressors and to generate variance of group activity inside the cage. Further exploration of noninvasive home cage motility combined with main physiological indicators might help us to assess the effectiveness of a new enrichment strategy

By 2040 Alzheimer’s disease (AD) will affect approximately 107 million people worldwide (PMID: 19595937). Studies show that hypertension, diabetes, atherosclerosis and obesity are risk factors for both vascular disorders such as stroke and AD (PMID:25096624). Risk of stroke increases with aging and AD is more common in elderly (PMID:23303851). Emerging evidence shows that stroke increases the risk of developing AD and in return, AD is a risk factor for stroke (PMID:25096624). But exact mechanisms behind this correlation are unknown and remain to be investigated. To understand underlying mechanisms of stroke on AD pathophysiology and sex-specific differences, we investigated the effect of ischemic stroke on female and male double transgenic APPSWE/PS1ΔE9 (AD) and C57BI/6 wild type (wt) mice from 4 months until 12 months of age. Mice were subjected to transient occlusion of the right middle cerebral artery (tMCAo) to induce an ischemic stroke.

Before the stroke induction baseline measurement of general health parameters (e.g, body weight, blood pressure) and motor skills (e.g. activity, strength, coordination) were measured. After stroke induction, these measurements are being repeated at several time points along with MRI measurements (e,g, rsfMRI, DTI, MRS, FAIR-ASL) to assess the effect of stroke on brain structure, function and connectivity. Results from the behavioral and imaging experiments will be presented and are currently being analyzed. Digital ventilated cages (DVC, Tecniplast) system was used to study individual locomotion via calculation of DVC metric measures (activity, walked distance, walked velocity, total turnings, laterality index) 24/7 before and after surgery. Especially Stroke APPs mice walked more than sham mice. This study will help to elucidate mechanisms of stroke on AD pathophysiology and sex-specific differences to stimulate the development of tailor-based treatment strategies.

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The key elements in performing animal experiments and fulfilling the mandate “Replace, Reduce and Refine” are robustness and reproducibility. However, animals including mice represent highly complex experimental subjects open to many variables. Here we describe the use of a Digital Ventilated Cages (DVC) system which continuously records home-cage animal motion and diurnal rhythms.

We show that such a system can reliably detect rapid cage activity changes occurring over 24hr where animals are added or removed from the cages. Further, using an Amyotrophic Lateral Sclerosis (ALS) mouse model cohoused with genetically matched wild type mice, we show with data collected for ~12 weeks before ALS disease manifestation and then during disease progression, that the DVC system can detect slower subtle behavioral changes occurring over weeks in the ALS mice.

We demonstrate that such automated cage data collection systems have the potential to refine or augment daily welfare checks, monitor animal experimentation in progress and assist in their interpretation. This project represents an innovative approach that provides a higher quality of animal husbandry and experimental reproducibly.

The behavior of laboratory rats and mice has been a topic of study for more than half a century, for applications ranging from welfare and health monitoring or phenotyping of mutants to CNS drug discovery, safety pharmacology and toxicology. Conventionally, laboratory rodents spend their life in a home cage in a rack in a vivarium, from which they are taken to an experimental arena to engage in a behavioral test, after which they return to their home cage. Handling and transportation of the animals can lead to stress and the introduction into a test apparatus typically leads to a novelty response, both of which can impact the behavior being measured. A short-lasting observation in a test apparatus is little more than a snapshot of the life of the animal, which spends most of its time in the home cage, outside the researcher’s attention. Furthermore, the great variety of arenas and apparatus (in terms of material, size, design, etc.) that are used for a particular test paradigm, combined with lack of standardization regarding test protocols and environmental factors, contributes to the low reproducibility of behavioral experiments, as has been widely documented in publications during the past decade. For these reasons, there is a growing consensus among researchers of animal behavior that rather than bringing the animal to the experiment, we should bring the experiment to the animal. That is, create an instrumented home cage environment in which the spontaneous behavior of rodents and their responses to interventions and stimuli can be monitored in a fully automated manner, 24/7, in a semi-natural environment.

Noldus Information Technology’s answer to this challenge is the PhenoTyper®, a versatile and modular test cage that can be furnished as a home cage, in which animals can reside for days, weeks or months, while behavioral data are collected continuously through the built-in infrared video camera and other sensors. Using the EthoVision® software for data acquisition and analysis, a large number of behavioral read-outs can be computed to quantify the animal’s spontaneous behavior (e.g. activity level, sleep/wake rhythm, locomotion, exploration, eating, drinking) and to assess learning, memory, attention, anxiety and other brain functions using automated stimulus/response protocols. The overhead camera allows automated recording of body postures and behavior patterns such as rearing, grooming, sniffing, head twitching, and object recognition. Modern AI techniques such as deep learning enable us to increase the accuracy and robustness of these measurements. Current R&D focus is on software- and hardware-based solutions for studies of social behavior with multiple animals in a single PhenoTyper cage.

Besides supporting a wide range of behavioral test paradigms, the PhenoTyper has become a platform for multimodal measurements, with concurrent recording of locomotion, ultrasonic vocalizations, physiology and brain activity. This trend is enabled by advances in wireless telemetry, miniaturization of sensors, computer vision and machine learning algorithms, and real-time computing power. Collaboration with other manufacturers has resulted in a range of integrated solutions with, e.g., optogenetic stimulation, in-vivo calcium imaging, or EEG recording in freely behaving animals. Multimodal measurements lead to more meaningful outcome parameters, easier detection of errors and refinement of animal tests.

TSE was the first company to bridge the gap between animals living in the home cage versus animals in an experimental (read =human) setting. Under the motto, bring the experiment to the animal, we build 3 technology platforms to realize this vision: PhenoMaster (Metabolism), Intellicage (Behavior), and Stellar telemetry (Physiology). In this presentation, I will provide insight into the integration of these technologies around home cages. Moreover, we are now working towards an even higher level of integration is a concept that we call “PhenoWorld” in which colonies of mice are living together while unbeknownst to them some can be asked to perform specific tasks, some can be “treated,” or some can have a different genetic background. By using the normal colony as a standard, subtle phenotypes can be picked up against a solid, reproducible background. A family of interconnected “home cages” is used to create a home with a “living room,” “food court”, “fitness studio” and even a “bedroom” where animals can retreat.

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Weizmann selected mile stones on innovations:

• In 1941, Dr. Weizmann established the first pharmaceutical company in Israel,
• The Weizmann Institute of Science was the first to introduce cancer research in Israel and the first to build particle accelerators.
• The Institute was the first to establish, in 1959, a technology transfer company, YEDA.
• Israel’s first drug, Copaxone®, developed at the Weizmann Institute of Science, received FDA approval in 1997.
• The Institute established the first hi-tech park in Israel, adjacent to the campus.

The best example of the Institute’s approach to innovation was the WEIZAC project. WEIZAC, was the first computer in Israel and the third in the world, was built at the Weizmann Institute during 1954-1955. Dr. Chaim Weizmann assigned $50,000 for the project (20% of the Weizmann Institute total budget…) There are several innovative techniques existing already today related to animal management and husbandry. Examples are from the meat production and milk production which monitor both the health, ethics and production. The DVC which was developed lately can play a major role In the field of Laboratory Animals. Specifically, in ethics and welfare.

The present capabilities and hopefully future ones (adding cameras, machine learning and Artificial intelligence) can give us indications on housing and wellbeing of mice and rats and health assessment such as appearance, body conditions, environmental conditions, behaviors and procedure-specific indicators for a specific study.

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In an animal facility in which approximately a third of mouse cages are equipped with DVC, Dr. Honetschläger presented the return of interest (ROI) of using the DVC for managing the facility. Results showed a reduction in cage change interval, increased animal welfare (cage change is stressful if not needed) and personnel time savings.

In the work presented, Dr. Lerat showed the impact of latrine position and ammonia (NH3) levels on mouse locomotor activity. Especially in male C57BL6J mice (cage change every 2 weeks), the ammonia increased above 100 ppm if the latrine was on the rear of the cage. Locomotor activity measured considerably decreased in the same area (discomfort of the animals), raising the question of food and water ad libitum access. No impact on body weight was observed, but further experiments are needed to evaluate the impact on the animal physiology.

Ian Welch presented the implementation of Mosaic, a new laboratory software management system, at the University British Columbia and its affiliates. Mosaic has proved to be a very stable, robust and agile system. The agility of the system along with its multiple utilities has made it an ideal platform to help harmonize practices across multiple operational lines including colony management, compliance issues and now business and procurement processes. The flexibility of the DVC software has been demonstrated to integrate well into MOSAIC.

Leveraging the latest web designs and tools to develop and deploy an animal facility management (cloud based) solution that can adapt to the unicity of each facility, and integrate data from digital sources such as Tecniplast DVC to improve efficiencies and provide valuable insights.

Nagano is a protocol management and animal management system software with the most advanced DVC® integration on the market. Nagano’s vision is the best and updated information can be reached through integration of protocol, animal information and welfare in one place.

At a-tune we believe that connecting digital technologies enhances processes, reduces error and can help to enhance animal welfare. a-tune provides a complete integrated animal management software solution to allow the capture, storage and effective retrieval of your data. tick@lab enhances data flow and automates processes. It offers controlled user access, streamlined communication and real time data entry and recovery. By digitalising our environment and connecting with existing and newly developed technologies, we can close the gaps in disjointed data transfer. We can further automate and improve our processes whilst reducing manual data entry to give back, more time to science.

Using video software analysis, Laura presented the capabilities of Vium Home Cage monitoring system. Through the analysis (cloud based), mouse models such as multiple sclerosis and lung carcinoma could be better characterized and described in their home cage.

The purpose of this project is to understand if and how microglia, the resident immune cells of the nervous system, contribute to the regulation of sleep and circadian behavior. To this aim, microglial mRNA expression and morphology are analyzed during the light-on and light-off phases. Moreover, possible alterations of circadian behavior are investigated in mice with modified microglia cells. The DVC® system by Tecniplast is used to evaluate mice motor activities and to modulate the light-night cycle in the different experimental conditions, limiting animal manipulation and increasing the data sets per single experiments. Moreover, the modulation of light-dark cycle is evaluated in red and black cages in the DVC® system by analyzing the circadian motor activity.

In a mouse model of ischemic stroke, Klara showed clearly the beneficial effects of voluntary exercise. She showed that mice with a stroke which had free access to running wheels displayed increased activity and locomotion when compared to non-running wheel stroke animals. Furthermore, voluntary exercise improved the functional connectivity in the brain one week after stroke.

The research group of the department of Anatomy at the Radboud university medical center investigated the effect of different diets as therapeutic approach directly after stroke on regaining motor and cognitive functioning, MRI parameters, neuroinflammation, and neurogenesis. They employed Hydroxytyrosol (HT, foremost phenolic component of extra-virgin olive oil) and Fortasyn (comprising docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium) to study if any beneficial effects could be observed on the aforementioned parameters. In female Fortasyn-fed stroke mice impairments activity and motor skills were not improved, while DVC was able to show recovery of walked distance in all stroke mice. Notably, in stroke mice on an HT diet showed increased strength in the forepaws, as well as improved short-term recognition memory probably due to improvement in functional connectivity. Here, DVC analysis showed a laterality (side preference to turn) at post-surgery week 2 in all stroke mice at night.