3 Minute 3Rs December 2019

3 Minute 3Rs

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The December episode of 3 Minute 3Rs, brought to you by the NC3Rs (www.nc3rs.org.uk), the North American 3Rs Collaborative (www.na3rsc.org), and Lab Animal (www.nature.com/laban).Papers: 1. Cage aggression in group-housed laboratory male mice: an international data crowdsourcing project. https://www.nature.com/articles/s41598-019-51674-z2. Towards animal-free neurotoxicity screening: Applicability of hiPSC-derived neuronal models for in vitro seizure liability assessmenthttps://www.altex.org/index.php/altex/article/view/13213. Optimal solid state neurons https://www.nature.com/articles/s41467-019-13177-3[NC3Rs] Mice are social creatures. It's why we house them in groups in the lab to improve their welfare and allow the animals to make social interactions that simply aren't possible if they're individually housed. However, the social groupings mice make in the wild are complex, with hierarchies of social dominance. In the lab group has mice are kept in cages, which means dominant and subordinate males must stay in close quarters, which can lead to aggression related stress and injuries. To better understand this welfare concern, the NC3Rs have used a crowdsourcing approach, engaging with lab technicians worldwide to estimate the prevalence of male mouse aggression. Data from over 100,000 mice in over 45,000 cages was submitted for analysis, which has been published last month in Scientific Reports.The publication by Lidster et al. recommends small practical husbandry changes such as spot cleaning cages or transferring nesting material to minimize male mouse aggression. You can find out more in the link in the description. [NA3RsC] While drug approval rates are on the rise, only about 10% of drugs in phase 1 development will gain full approval. One of the causes of drug attrition is drug-induced seizures; There is a need for more translational in vitro alternatives to predict seizure liability. Here, the authors evaluated three human induced pluripotent stem cell (hiPSC)-derived neuronal models. All models demonstrated development of functional neuronal networks that exhibited parameters linked to seizure-like events in vivo. These parameters were then modulated with three compounds known to induce seizures. Differences in sensitivity were found between the models. Yet, compared to rat primary cortical neurons, the in vitro models were equally, or better able to detect seizureogenicity. While the authors recommend more compounds be tested and the available models further characterized before serving as full replacement, this data indicates the potential of these in vitro models as initial screening tools for seizure liability assessment which could lead to reduced animal use requirements. [LA] Neurons transmit electrical signals – so too do silicon chips. Moving that in vivo function in silico has long been a goal of many neuroscientists, but biological neurons are complex, and their electrical properties and nuances have been difficult to predict and mimic artificially. That hasn’t stopped researchers from trying. A team led by Alain Nogaret at the University of Bath recently made progress, presenting artificial neurons on a silicon chip that matched the patterns of rat neurons with over 90% accuracy. It took lots of mathematical modeling, derived equations, and tweaking, but the team was able to optimize the chips so that they relayed electrical signals in the non-linear fashion that’s characteristic of biological neurons, all with considerably less power required than prior attempts. The design details and rat neuron comparisons can be found in the journal Nature Communications.

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