Could Ultrasonic Vocalisations Provide The Elusive, Graded Measure Of Affective State Needed To Inform Refinements For The Laboratory Rat?

超声波发声能否提供难以捉摸的、分级的情感状态测量，以通知实验室老鼠的改进？

• 批准号: NC/Y00082X/1
• 负责人: Emma Robinson
• 金额: $ 75.71万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FY00082X%2F1
• 关键词: Could; Ultrasonic; Vocalisations; Provide; Elusive

Animal research requires that studies consider the 3Rs (Reduce, Refine and Replace). Refinement involves using methods which cause the least suffering to the animal, and this can be more challenging to assess objectively. To achieve refinement requires the ability to quantify the animals affective or 'emotional' experience. Although overt changes in the animal's behaviour can provide some information, these do not offer sufficient sensitivity to understand the emotional impacts. Our research has pioneered the development of objective methods to measure animals' affective state. By translating behavioural methods from human psychology, we have developed and validated novel assays which accurately measure animals positive or negative affective experience of different interventions. We have used one of these assays, the affective bias test, to demonstrate that high frequency calls emitted by rats provide a graded measure of their individual emotional experience. This raises the exciting possibility that measuring these ultrasonic vocalisations may provide a simple and easy to use method to evaluate refinements. Our approach will not require costly equipment or specialist expertise meaning it could be readily set-up and utilised within any animal research facility.Previous studies suggest that adult rats emit 50kHz or 22kHz calls when they experience putative positive or negative events, respectively. Although indirect evidence to support this idea has been achieved, we have not previously had a reliably objective method to accurately quantify the relationship between these calls and the animal's individual affective experience. Direct correlation between these ultrasonic vocalisations and affective state has so far only been tested in relation to human simulated play or 'tickling' in rats. The affective bias test is a simple, reward-based task which we have shown can provide a graded measure of the affective state of rats during acute psychosocial or pharmacological interventions. The task measures affective biases related to associative learning and memory. Affective bias describes the effect of emotional state on different cognitive processes and are known to modulate learning and memory and decision-making behaviour in human and non-human animals. Cognition can be biased in either a positive or negative direction influenced by both short-term changes in emotional state and arising from changes in core affect akin to mood. Using our affective bias test, we will test the hypothesis that ultrasonic vocalisations can provide an equally sensitive measure of animal's affective state but using a method which can be widely adopted across the scientific community. Our studies correlating calls with our measure of positive or negative affective state in the ABT will provide direct evidence of the validity of the approach. We will also test a cohort of animals in a putative depression-like state where we have found that negative affective biases are potentiated. Our aim is to establish whether vocalisations are similarly altered and hence provide a way of understanding animals core affective state. These validation studies will tell us whether recording animals calls can provide information about their emotional state both during acute experiences and in relation to core affect or 'mood'. In our final work package, we will translate the approach to testing in the home-cage and at an individual and populations level in response to manipulations commonly used the laboratory. We will also test two refinement methods, habituation to human handling and a novel caging system designed to increase space and social interactions whilst also being practical for handling. The outcomes of this project will be methods to enable many more researchers to study refinement and enable institutions to monitor the affective state of their colonies using a simple, non-invasive and non-specialist method.

动物研究要求研究考虑3RS（减少，完善和替换）。精炼涉及使用对动物造成最少苦难的方法，这可能更具挑战性地评估。为了实现改进，需要能够量化动物情感或“情感”体验的能力。尽管动物行为的明显变化可以提供一些信息，但这些信息不能提供足够的敏感性来理解情感影响。我们的研究率先开发了衡量动物情感状态的客观方法的发展。通过翻译人类心理学的行为方法，我们已经开发了和验证了新的新试验，这些测定方法可以准确地测量不同干预措施的积极或负面情感经验。我们已经使用了其中一种测定法，即情感偏见测试，以证明大鼠发出的高频调用提供了对其个人情感体验的分级度量。这增加了令人兴奋的可能性，即测量这些超声波发声可能会提供一种简单易于使用的方法来评估改进。我们的方法将不需要昂贵的设备或专业知识，这意味着它可以很容易地进行设置并在任何动物研究设施中使用。提出的研究表明，当成年大鼠分别经历了假定的积极或负面事件时，成年大鼠会发出50kHz或22kHz。尽管已经实现了支持这一想法的间接证据，但我们以前没有一种可靠的客观方法来准确量化这些呼叫与动物的个人情感经验之间的关系。到目前为止，这些超声波发声与情感状态之间的直接相关性仅在大鼠中的人类模拟游戏或“挠痒”中进行了测试。情感偏见测试是一项简单，基于奖励的任务，我们显示的可以在急性社会心理或药理干预期间提供对大鼠情感状态的分级度量。任务衡量与关联学习和记忆有关的情感偏见。情感偏见描述了情绪状态对不同认知过程的影响，并且已知可以调节人类和非人类动物的学习，记忆以及决策行为。认知可能会受​​到正向或负面方向的偏见，该方向受情绪状态的短期变化以及核心变化产生的影响类似于情绪的影响。使用我们的情感偏见测试，我们将检验以下假设：超声波发声可以提供对动物情感状态的同样敏感的衡量，但使用可以在整个科学界广泛采用的方法。我们的研究将呼吁与ABT中正面或负面情感状态的量度相关联，将提供该方法有效性的直接证据。我们还将在假定的抑郁症状态下测试一群动物队列，在该状态下，我们发现负面情感偏见受到增强。我们的目的是确定发声是否被类似地改变，因此提供了一种理解动物核心情感状态的方式。这些验证研究将告诉我们记录动物的呼叫是否可以在急性体验和与核心影响或“情绪”有关的情况下提供有关其情绪状态的信息。在我们的最终工作包中，我们将根据通常使用的实验室的操纵来翻译家庭式和人群和人群级别的测试方法。我们还将测试两种改进方法，人类处理的习惯以及一种新颖的笼子系统，旨在增加空间和社交互动，同时也对处理也很实际。该项目的结果将是使更多的研究人员能够使用简单，非侵入性和非专业主义方法来研究其殖民地的情感状态的方法，并使机构能够监测其殖民地的情感状态。