Welfare assessment of rhesus macaques: from field observation to computational models of brain network

在伦理和法律上，研究活脊椎动物的生物学家有义务优化研究对象的身体和情感福利，改进饲养和实验程序，将疼痛、痛苦、痛苦或持久伤害的可能性降至最低。参与神经科学实验的非人类灵长类动物的福利尤其令人担忧。非人灵长类动物可能最有可能经历与人类相似的痛苦，因为它们在分类学上与人类相似，而对非人类灵长类动物进行的神经科学实验往往会持续多年，这增加了人们对实验和饲养程序潜在累积影响的担忧。目前用于评估非人类灵长类福利的方法是不够的。该项目的目标是开发新的灵长类动物福利行为指标，该指标对动物经历的持久情感状态的价态很敏感，并且易于在各种环境(学术和工业环境)中进行评估。我们将关注猕猴，这是神经科学实验中最常见的灵长类物种。恒河猴生活在一个高度等级的社会中，不同的等级与不同水平的慢性压力有关。该项目的第一个目标是评估在卡约圣地亚哥(波多黎各)自由放养的恒河猴种群中，行为的详尽清单如何随等级等级而变化，以确定行为福利指标的潜在候选者(第一年)。然后，学生将测量参与纽卡斯尔神经科学实验的恒河猴预先筛选的行为的频率，并使用我们最近验证的神经成像方法确认与这些行为相关的情感状态的有效性(二年级)。为了进一步了解与猕猴行为相关的情感状态的性质，学生将把与这些行为相关的结构和活动与人类几种情感障碍(例如，严重抑郁、创伤后应激障碍、双相情感障碍)相关的大脑网络进行比较(3年级)。最后，学生将调查哪些实验和饲养程序可能导致不同行为频率的变化(4年级)。该项目将利用我们在世界上独一无二的持续纵向数据库，该数据库结合了两年一次的健康猕猴大脑的结构(T1、T2和DTI)和功能(静息状态)MRI扫描，家庭笼养行为的视频记录，血液和毛发样本，以及健康和暴露于科学和畜牧业程序的详细记录。将使用生活在圣地亚哥岛上的自由放养猕猴的现有视频记录，结合它们的身份、年龄、性别和等级等级记录，对猕猴福利的候选行为指标进行预筛选。为了更好地了解这些视频，这名学生将在圣地亚哥卡约岛呆上两周，观察自然环境中的猕猴群体。因此，学生身份将提供一个独特的机会，从现场观察到大脑网络的计算模型来研究灵长类动物的福利。该项目符合BBSRC的战略优先事项“管理动物的福利”和“利用动物进行研究的3R”。它将允许博士生发展结合动物行为和福利、活体整体生理学和定量技能的跨学科技能。

Biologists working with live vertebrates are ethically and legally obliged to optimise the physical and emotional welfare of their subjects, refining husbandry and experimental procedures to minimise the potential for pain, suffering, distress or lasting harm. The welfare of non-human primates involved in neuroscience experiments is of particular concern. Non-human primates perhaps have the greatest potential to experience human-like suffering due to their taxonomic proximity to humans, and neuroscience experiments on non-human primates often last for many years, increasing concerns about potential cumulative effects of experimental and husbandry procedures. Methods currently used to assess non-human primate welfare are inadequate. The goal of this project is to develop new behavioural indicators of primate welfare which are sensitive to the valence of enduring affective states experienced by the animal and which are easy to assess in various settings (academic and industrial settings). We will focus on rhesus macaques, the most common primate species used in neuroscience experiments. Rhesus macaques live in a highly hierarchical society, with different ranks associated with different levels of chronic stress. The first objective of this project is to assess how an exhaustive list of behaviours varies with hierarchical ranks in a free-ranging population of rhesus macaques in Cayo Santiago (Puerto Rico) to identify potential candidates for behavioural welfare indicators (year 1). The student will then measure the frequency of the pre-screened behaviours in rhesus macaques involved in neuroscience experiments at Newcastle and confirm the valence of the affective state associated with these behaviours using the neuroimaging approach we have recently validated (year 2). To gain further insight into the nature of the affective state associated with macaque behaviours, the student will then compare the brain networks whose structure and activity covary with these behaviours with those involved in several affective disorders in humans (e.g. major depression, post-traumatic stress disorder, bi-polar disorder) (year 3). Finally, the student will investigate which experimental and husbandry procedures might be responsible for the variation in the frequency of different behaviours (year 4). This studentship will take advantage of our on-going longitudinal database, unique in the world, that combines biannual structural (T1, T2 and DTI) and functional (resting-state) MRI scans of healthy macaque brains, video recordings of home-cage behaviour, blood and hair samples and detailed records of health and exposures to scientific and husbandry procedures. Pre-screening of candidate behavioural indictors of macaque welfare will be done using existing video-recordings of free-ranging macaques living on Cayo Santiago Island, combined with records of their identity, age, sex and hierarchical ranks. In order to put the video collection into perspective, the student will spend two weeks at Cayo Santiago observing social groups of macaques in their natural environment. As such, the studentship will offer a unique opportunity to study primate welfare from field observations to computational models of brain networks. This project fits the BBSRC strategic priorities 'Welfare of managed animals' and '3Rs in research using animals'. It will allow the PhD student to develop interdisciplinary skills combining animal behaviour and welfare, whole organism in vivo physiology and quantitative skills.