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.

小鼠是广泛使用的模式生物，也是其本身的迷人主题。该团队由三位高影响力的神经科学家组成，他们使用小鼠作为模型，由备受推崇的动物福利研究人员领导，他们研究了住房（例如笼子富集）对实验室小鼠健康的影响。** 我们需要设备来量化小鼠的惊吓反射（对突然的厌恶刺激（如响亮的声音）的快速反应），以评估焦虑，听力能力和感觉门控作为我们四个研究项目的组成部分。在啮齿类动物的研究中，惊吓反应是焦虑和恐惧的标准检测方法。它们也被广泛用于评估前脉冲抑制（PPI）：重要的是因为它捕获了“感觉门控”，大脑过滤不相关信息的能力。因此，我们需要现代化的小鼠专用惊吓装置来评估焦虑（Mason & Choleris Labs），以调查例如小鼠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屏幕，以了解特定激素，神经递质和“DREADD”操作的任何明显影响（例如对社会学习，跨模态物体识别或前额叶任务的表现），实际上是通过“低水平”感觉处理效应（Choleris，Winters & Bailey Labs）。此外，梅森实验室正在测试PPI作为持续（不适当的重复）的代理：刻板行为的可能相关性（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，由于许多品系的实验室小鼠都容易出现早发性听力损失-当使用惊吓幅度来推断焦虑或PPI来评估感觉门控时，这是一种潜在的混淆-该设备还具有“触觉功能”（空气抽吸设施），这意味着它的使用不依赖于通常的仅声学出厂默认设置。 这将使我们所有人都能够从焦虑和感兴趣的感觉门控效应中评估和解析出听力损失的任何混淆效应（如果任何小鼠被证明完全失聪，甚至可以使用惊吓和PPI的完全触觉功能）。最后，使用声学惊吓作为一种方便的，非侵入性的方式来评估小鼠的听力能力，将使梅森实验室能够测试新的假设，即标准饲养的雌性小鼠比富集饲养的小鼠更具攻击性，因为它们过早地失去了听力。** 在5年内，该设备将训练C。89 HQP。但我们估计这些设备将持续10年，因此可能会培训两倍的人数。我们还估计，在我们的四个实验室中，每月总共将使用80小时。