Startle reflex apparatus: a flexible system for assessing anxiety, hearing ability and sensory gating in mice

惊吓反射装置：用于评估小鼠焦虑、听力和感觉门控的灵活系统

• 批准号: RTI-2019-00101
• 负责人: Mason, Georgia
• 金额: $ 3.13万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658970
• 关键词: Startle; reflex; apparatus; flexible; system

Mice are widely-used model organisms and fascinating subjects in their own right. This team comprises three high impact neuroscientists who use mice as models, led by highly-regarded animal welfare researcher who studies effects of housing (e.g. cage enrichment) on laboratory mouse well-being. ******We need equipment to quantify startle reflexes in mice (rapid responses to sudden aversive stimuli like loud tones), in order to assess anxiety, hearing abilities and sensory gating as an integral part of our four research programmes. In rodent-based research, startle responses are standard assays for anxiety and fear. They are also widely-used for assessing prepulse inhibition (PPI): important because this captures ‘sensory gating', the brain's ability to filter out irrelevant information. We therefore need modern, mouse-dedicated startle apparatuses to assess anxiety (Mason & Choleris Labs), to investigate for example how mouse housing affects their welfare, and how early neuroendocrine events influences their affective states. We also need to assess PPI, as an important screen in cognitive tests for understanding whether any apparent effects (e.g. on social learning, cross-modal object recognition, or performance in prefrontal tasks) of the specific hormones, neurotransmitters and ‘DREADD'-manipulations to be studied, are actually acting instead via 'low-level' sensory processing effects (Choleris, Winters & Bailey Labs). In addition, PPI is being tested by the Mason Lab as a proxy for perseveration (inappropriate repetition): a likely correlate of stereotypic behaviour (a widely-used animal welfare indicator whose neurobiological bases are still little understood).******Crucially, since many strains of lab mice are prone to early-onset hearing loss -- a potential confound when using startle amplitudes to infer anxiety or PPI to assess sensory gating -- this apparatus also has 'tactile functions' (an air puff facility), meaning that its use does not rely on the usual acoustic-only factory default settings. This will allow us all to evaluate and parse out any confounding effects of hearing loss from the anxiety and sensory gating effects of interest (and even to use fully tactile functions for startle & PPI if any mice prove to be fully deaf). Finally, using acoustic startle as a convenient, non-invasive way to assess mouse hearing abilities will allow the Mason Lab to test novel hypotheses that standard-housed female mice are more aggressive than mice in enriched housing because they lose their hearing prematurely. ******In 5 years the equipment will train c. 89 HQP. But we estimate the equipment will last 10 years, so potentially training twice that number. We also estimate it will be used for 80 hours/month in total across our four labs.

老鼠是被广泛使用的模式生物，也是其本身令人着迷的研究对象。该团队由三位高影响力的神经科学家组成，他们以小鼠为模型，由备受尊敬的动物福利研究员领导，他们研究住房（例如笼子浓缩）对实验室小鼠健康的影响。******我们需要设备来量化老鼠的惊吓反射（对突然的厌恶刺激，如大声的声音的快速反应），以便评估焦虑，听力能力和感觉门控，作为我们四个研究项目的组成部分。在以啮齿动物为基础的研究中，惊吓反应是焦虑和恐惧的标准检测。它们还被广泛用于评估脉冲前抑制（PPI）：这很重要，因为它捕捉到了“感觉门控”，即大脑过滤掉无关信息的能力。因此，我们需要现代的、专门用于老鼠的惊吓装置来评估焦虑（梅森和霍乱实验室），以调查例如老鼠的住房如何影响它们的福利，以及早期神经内分泌事件如何影响它们的情感状态。我们还需要评估PPI，作为认知测试中的一个重要筛选，以了解所研究的特定激素、神经递质和“恐惧”操作是否有任何明显的影响（例如，在社会学习、跨模式物体识别或前额叶任务中的表现），实际上是通过“低水平”的感觉处理效应而起作用（Choleris， Winters & Bailey实验室）。此外，梅森实验室正在测试PPI作为持久性（不适当的重复）的代表：一种可能与刻板行为相关的行为（一种广泛使用的动物福利指标，其神经生物学基础仍然知之甚少）。******至关重要的是，由于许多实验室小鼠容易出现早发性听力丧失——当使用惊吓幅度来推断焦虑或PPI来评估感觉门控时，这是一种潜在的困惑——这种装置还具有“触觉功能”（一种吹气装置），这意味着它的使用不依赖于通常的只有声音的工厂默认设置。这将使我们所有人都能评估和分析出听力损失带来的任何混淆效应，包括焦虑和感兴趣的感觉门控效应（如果有任何老鼠被证明是完全失聪的，甚至可以使用完全触觉功能来检测惊吓和PPI）。最后，使用声惊吓作为一种方便的、非侵入性的方法来评估老鼠的听力能力，将允许梅森实验室测试新的假设，即标准饲养的雌性老鼠比强化饲养的老鼠更具攻击性，因为它们过早地失去了听力。******在5年内，该设备将培训89hqp。但我们估计这些设备将使用10年，所以训练人数可能是这个数字的两倍。我们还估计它将在我们的四个实验室中每月总共使用80小时。