Naturalistic and translational decision making assays

自然和转化决策分析

• 批准号: 2898179
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-2898179
• 关键词: Naturalistic; translational; decision; making; assays

Decision making is a crucial aspect of everyday life for all animals. From lower-level perceptual and perceptuo-motor guided decisions about whether and when to cross a road (humans) or choosing an escape or foraging path (animals) to higher-level decisions about selecting a suitable habitat (animals) or buying a house (humans). While some decisions are only relevant for humans (e.g. buying a house) many others are common to different mammalian species (e.g. choosing on the best course of action to avoid immediate threats or navigate an unfamiliar environment). Such decisions are likely to be similarly affected by internal states such as anxiety and stress and personality traits such as cognitive flexibility and tendency towards addiction. Understanding human DM and, in particular, how factors such as stress and/or clinical disorders might impact upon DM is critical. To fully understand mechanisms of DM in human requires us to consider both behaviour and how this links to the neuronal substrates that drive this behaviour. Revealing the detailed neuronal substrate can only be achieved in experimental animals in which recording and manipulation of specific neuronal circuitry can be performed. A key challenge then is to establish appropriate behavioural assays that can be reliably translated between humans and rodents.In this project we will develop a range of principled decision-making tasks that are comparable for animals and humans. Human tasks will take advantage of Virtual Reality (VR) technologies available in the Virtual Reality Research (VR2) Facility at the University of Manchester (https://sites.manchester.ac.uk/VR2/). VR enables us to place the human in a virtual real-world DM tasks while retaining control of key experimental variables. In addition in VR it is possible to impose realistic stressors on the human to mimic equivalent tasks in rodents. Rodent tasks will be performed in real physical environments adapted to match parameters of the human tasks. We anticipate that the findings from this project will be important for laying down a testbed of paradigms for future investigation of neural substrates of DM and eventually developing neural-based models of altered decision making (e.g. in addiction) to underpin novel treatments.This work fits within the BBSRC's Theme: Advancing the Frontiers of Bioscience Discovery under the Understanding the Rules of Life subheading. We will be addressing basic questions regarding the nature of choice in both humans and rodents. In addition, the research has the potential to underpin future research within the strategic challenge: Bioscience for an Integrated Understanding of Health. Understanding the mechanisms of choice (both cognitive, perceptual and perceptuo-motor) has implications for individuals and clinical groups in which such processes are altered (e.g. in addiction). This work is necessary to enable us to develop neural models of altered decision making in such groups and may underpin future treatments for these conditions. This project will benefit from an in vivo skills supplement to enable us to understand behaviour and motor strategies (via visuo-motor and head/body and eye movement). These will be measured during free movement to determine which part of the visual environment is captured by animal retinae. Achieving this will enable to understand how rodents position their eyes to detect salient visual stimuli (e.g. an approaching predator), how they coordinate eye movements with spontaneous behaviours such as locomotion and rearing and how such motor decisions are driven by parameters of the environment. Under the in vivo training component the student will develop skills in: Chronic implantation of miniature cameras for tracking eye movements in freely moving animals Behavioural tests of visually guided behaviours paired with recordings of eye and head/body movements

对所有动物来说，决策是日常生活中至关重要的一个方面。从较低层次的知觉和知觉-运动引导的是否以及何时横穿马路(人类)或选择逃跑或觅食的路径(动物)的决策，到更高层次的关于选择合适的栖息地(动物)或购买房子(人类)的决策。虽然有些决定只与人类有关(例如买房子)，但其他许多决定对不同的哺乳动物物种是共同的(例如，选择最佳行动方案以避免直接威胁或驾驭陌生环境)。这样的决定很可能同样会受到焦虑和压力等内在状态以及认知灵活性和成瘾倾向等个性特征的影响。了解人类糖尿病，特别是了解压力和/或临床疾病等因素对糖尿病的影响是至关重要的。要完全了解人类糖尿病的机制，我们需要考虑行为以及这与驱动这一行为的神经元底物之间的联系。揭示详细的神经元底物只能在实验动物中实现，在实验动物中可以对特定的神经元电路进行记录和操作。因此，一个关键的挑战是建立适当的行为分析，可以在人和啮齿动物之间可靠地转换。在这个项目中，我们将开发一系列可与动物和人类相比较的原则性决策任务。人工任务将利用曼彻斯特大学(https://sites.manchester.ac.uk/VR2/).)虚拟现实研究设施中提供的虚拟现实(VR)技术VR使我们能够将人置于一个虚拟的现实世界中，在执行DM任务的同时，保持对关键实验变量的控制。此外，在虚拟现实中，有可能将现实的压力源施加到人类身上，以模仿啮齿动物的同等任务。啮齿动物的任务将在真实的物理环境中执行，以匹配人类任务的参数。我们预计，这个项目的发现将对为未来研究糖尿病的神经基础奠定范例的试验台，并最终开发基于神经的改变决策(例如，成瘾)的模型以支持新的治疗方法将是重要的。这项工作符合BBSRC的主题：在理解生命规则副标题下推进生物科学发现的前沿。我们将解决有关人类和啮齿动物选择的性质的基本问题。此外，这项研究有可能支持未来在战略挑战中的研究：生物科学促进对健康的综合理解。了解选择的机制(认知、知觉和知觉-运动)对于改变这些过程的个人和临床群体(例如，成瘾)具有重要意义。这项工作是必要的，使我们能够开发神经模型的改变决策在这些群体中，并可能支持未来的治疗这些情况。这个项目将受益于体内技能补充，使我们能够理解行为和运动策略(通过视觉运动和头部/身体和眼睛运动)。这些将在自由运动时进行测量，以确定动物视网膜捕捉到视觉环境的哪一部分。实现这一点将使我们能够理解啮齿动物如何定位其眼睛以检测显著的视觉刺激(例如，接近的捕食者)，它们如何将眼睛运动与自发行为(如运动和站立)协调起来，以及此类运动决定如何受到环境参数的驱动。在活体训练部分，学生将在以下方面培养技能：长期植入微型摄像机，用于跟踪自由移动的动物的眼睛运动行为测试与眼睛和头部/身体运动的记录相结合的视觉引导行为测试