Conventional husbandry and the welfare of laboratory mice: assessing and alleviating negative emotions, pessimistic moods, and cumulative stress

我计划的这一阶段将研究积极的动物福利如何促进复原力和健康长寿。我的愿景是全面了解积极和消极事件如何影响应激反应、行为正常和身体健康：这将改变我们评估和改善农场、实验室和动物园动物住房的方式。对于全球数十亿的动物来说，住房包括小型围栏，这些围栏具有成本效益，但几乎没有活动或刺激的机会。但是，正如大流行封锁所揭示的那样，在压力和心理健康方面，这种限制可能会有代价。例如，老鼠是生物医学研究中使用最广泛的脊椎动物，它们有很强的动力去完成许多在传统实验室“鞋盒”笼子里不可能完成的自然行为，甚至把比自己更重的东西推到“富含”允许这些活动的资源的笼子里。此外，与那些生活在高度富集的围栏中的小鼠相比，传统住房中的雌性小鼠对它们的笼子具有攻击性，在判断偏差的认知任务中“悲观”，对急性压力源的反应更强，容易出现重复刻板路线追踪等异常行为，寿命更短。因此，丰富的住房不仅减少了挫败感，还增加了积极的社会互动，抗压力能力和寿命。因此，为了激发实际的改变，我将用老鼠作为模型和有价值的福利增强研究对象，来调查贫瘠的住房系统是否会使动物抑郁；大脑中出现了什么问题，产生了刻板印象行为；什么是最好的方式来丰富住房；丰富的住房如何增强抗压力能力；以及为什么知足能促进健康长寿。为了做到这一点，一系列实验和数据荟萃分析将在一项独特的雄心勃勃的出生到衰老研究中达到高潮，以评估高/低饲养应激的终生累积效应。这项工作将测试关于情绪状态如何影响情绪的基本假设；情绪如何影响压力恢复能力；以及终身情绪和适应能力对身心健康的累积影响。它将为改进研究小鼠的饲养提供实用的建议，并提出创造性的新方法来减少侵入性的、痛苦的研究过程的危害。这将为加拿大制定世界领先的实验动物护理标准；并改善全球数千万研究啮齿类动物的福祉（甚至可能提高其研究数据的有效性）。由于老鼠是研究其他物种福利问题的好模型，它的发现也将使数以百计的应用行为学家、福利科学家和兽医受益，他们正在努力评估和改善其他管理物种的福利，通过解决一些几十年来的福利难题（如刻板行为的病因学），并通过量化好/差住房对身心健康的累积影响。

This stage of my program will investigate how positive animal welfare promotes resilience and a long, healthy life. My vision is a comprehensive understanding of how positive and negative events affect stress reactivity, behavioural normalcy and physical health: one that transforms how we assess and improve farm, laboratory and zoo animal housing. For billions of animals globally, housing comprises small enclosures that are cost-effective, yet provide little opportunity for activity or stimulation. But -- as pandemic lockdowns so revealed -- such restrictions can have a cost, in terms of stress and mental health. For example mice, the most widely used vertebrate in biomedical research, are highly motivated to perform many natural behaviours impossible in conventional laboratory `shoebox' cages, even pushing weights heavier than themselves to access cages `enriched' with resources allowing such activities. Furthermore, compared to those living in highly enriched enclosures, female mice in conventional housing are aggressive to their cagemates, 'pessimistic' in cognitive tasks for Judgement Bias, more reactive to acute stressors, prone to abnormal behaviours like repetitive stereotypic route-tracing, and shorter lived. Enriched housing thus does not just reduce frustration: it increases positive social interactions, stress-resilience and lifespan. To inspire practical change, I will therefore use mice, both as a model and worthy target for welfare-enhancing research, to investigate whether barren housing systems make animals depressed; what goes wrong within the brain to generate stereotypic behaviours; what the best ways are to enrich housing; how enriched housing can enhance stress resilience; and why contentment promotes a long, healthy life. To do this, a series of experiments and data meta-analyses will culminate in a uniquely ambitious birth-to-senescence study to assess the lifetime cumulative effects of high/low husbandry stress. This work will test fundamental hypotheses about how emotional states influence moods; how moods affect stress resilience; and the cumulative effects of lifelong moods and resilience on physical and mental health. It will generate practical recommendations for improved husbandry of research mice, and suggest creative new ways to reduce the harms of invasive, painful research procedures. This could generate world-leading lab animal care standards for Canada; and improve well-being for 10s of millions of research rodents used globally p.a (maybe even improving the validity of their research data). Since mice are great models for welfare issues in other species, its findings will also benefit hundreds of applied ethologists, welfare scientists and veterinarians striving to assess and improve welfare in other managed species, by solving some decades old welfare puzzles (such as the aetiology of stereotypic behaviour) and by quantifying the cumulative mental and physical health impacts of good/poor housing.