Novel freely moving monkey framework for the study of naturalistic behaviors

用于研究自然行为的新型自由移动猴子框架

• 批准号: 10665292
• 负责人: Byounghoon Kim
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665292
• 关键词: 3-Dimensional; 3D world; Animal Model; Animals; Area; Basic Science; Behavior; Behavioral; Binocular Vision; Biological Models; Brain; Brain region; Callithrix; Cells; Chiroptera; Chronic; Cognitive; Complex; Custom; Data; Development; Disease; Electrodes; Environment; Episodic memory; Eye; Eye Movements; Female; Future; Goals; Hand; Head; Health; Hippocampus; Histology; Home; Human; Impaired cognition; Investigation; Knowledge; Limb structure; Limbic System; Location; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Memory; Modeling; Monkeys; Motion; Motor; Neurons; Neurosciences; Penetration; Positioning Attribute; Primates; Process; Property; Reflex action; Reporting; Research; Research Personnel; Rodent; Sensory; Signal Transduction; Source; Specific qualifier value; System; Systems Integration; Technology; Testing; Traumatic Brain Injury; Update; Upper limb movement; Visual; Visual System; Work; behavioral study; cell type; cognitive capacity; cognitive function; data acquisition; design; environmental change; face mask; gaze; male; monocular; motor control; multisensory; nervous system disorder; neural; neural circuit; neural correlate; neuromechanism; neurophysiology; nonhuman primate; novel; paragon; restraint; skull implant; virtual reality; visual tracking; way finding; wireless

PROJECT SUMMARY/ABSTRACT Animals live in dynamic, ever-changing environments. As such, survival requires them to explore their environment and process the barrage of sensory signals to form predictions about what to expect and how to respond to incoming sensory information. The requisite neural processing for naturalistic behaviors is highly complex, requiring the coordination of multiple brain functions including multisensory processing, sensorimotor integration, cognitive functions, and motor planning and execution. Thus, to understand the neural basis for naturalistic behaviors, it is essential to simultaneously study the behavioral and neural activity of animal models under relatively unrestrained conditions. A paragon example of such work is the neuronal basis of navigation in rodents and bats. However, the cognitive capacities, dexterous hands, and front-facing visual systems of human and non-human primates (NHPs) make them uniquely capable of predicting and influencing their environments. For this reason, NHPs are an ideal animal model for investigating human-relevant brain functions during complex, naturalistic behaviors. Thus, the goal of the current proposal is to develop and vet a novel research platform for conducting naturalistic studies with NHPs using navigation as the model system. To date, significant technical barriers have precluded the development of a robust freely moving monkey (FMM) framework. Here, we propose to implement fully wireless behavioral and multichannel neuronal data acquisition with female and male rhesus monkeys (Maccaca mulatta) during the free exploration of an open-field FMM arena. We will use 3D motion capture technology to record head, body, and upper limb movements. A novel facemask that is custom-designed and individualized for each animal will be used to perform binocular eye tracking. In addition, a novel microdrive system that is magnetic resonance imaging compatible will be used to safely and simultaneously introduce electrodes into multiple deep brain regions of the limbic system, as well as precisely verify the recording locations without histology. The microdrive system and a mobile neurologger will be contained within the cranial implant, enabling tether-less recordings while the animal is within the FMM arena as well as the home enclosure. To vet the FMM framework, we propose to use a free foraging paradigm. We will specifically test if well-established navigational properties found in rodents and bats are conserved in NHPs. Importantly, we will explore whether the neural circuitry is also elaborated in the primate brain to leverage the binocular, front-facing visual system. In particular, we will study the gaze-related properties of neurons during naturalistic behavior. We highly anticipate that behavioral and neuronal data acquired through this novel research platform will be unprecedented, enabling a more complete understanding of naturalistic primate brain functions including spatial navigation, visual and vestibular sensory processing, and motor control. Critically, this proposal sets the stage for the FMM framework to become an unparalleled research platform for investigating primate brain function in normal and diseased states with high human translational value.

项目概要/摘要 动物生活在动态、不断变化的环境中。因此，生存需要他们探索自己的 环境并处理大量的感官信号，以形成关于期望什么以及如何做的预测 对传入的感官信息做出反应。自然行为所必需的神经处理是高度 复杂，需要协调多种大脑功能，包括多感觉处理、感觉运动 整合、认知功能以及运动规划和执行。因此，要了解神经基础 自然行为，有必要同时研究动物模型的行为和神经活动 在相对不受约束的条件下。此类工作的一个典型例子是导航的神经元基础 啮齿动物和蝙蝠。然而，人类的认知能力、灵巧的双手和前置视觉系统 非人类灵长类动物（NHP）使它们具有独特的能力来预测和影响其环境。 因此，NHP 是研究复杂的、与人类相关的大脑功能的理想动物模型。 自然主义行为。因此，当前提案的目标是开发和审查一个新颖的研究平台 使用导航作为模型系统对 NHP 进行自然研究。迄今为止，重大技术 障碍阻碍了强大的自由移动猴子（FMM）框架的开发。在此，我们建议 实现雌性和雄性恒河猴的完全无线行为和多通道神经元数据采集 猴子 (Maccaca mulatta) 在露天 FMM 竞技场自由探索。我们将使用 3D 运动 捕捉技术来记录头部、身体和上肢运动。定制设计的新颖面罩 并对每只动物进行个性化的双眼追踪。此外，一种新颖的微驱动器 与磁共振成像兼容的系统将用于安全地同时引入 将电极插入边缘系统的多个深层大脑区域，并精确验证记录位置 没有组织学。微驱动系统和移动神经记录仪将包含在颅骨植入物内， 当动物处于 FMM 竞技场以及家庭围栏内时，可以进行无绳录音。审查 在FMM框架中，我们建议使用自由觅食范式。我们将专门测试是否完善 在啮齿动物和蝙蝠中发现的导航特性在 NHP 中得以保留。重要的是，我们将探讨是否 灵长类动物大脑中的神经回路也经过精心设计，以利用双目前置视觉系统。 特别是，我们将研究自然行为期间神经元与凝视相关的特性。我们高度 预计通过这个新颖的研究平台获得的行为和神经元数据将是前所未有的， 能够更全面地理解自然灵长类动物的大脑功能，包括空间导航， 视觉和前庭感觉处理以及运动控制。至关重要的是，该提案为 FMM 奠定了基础 框架成为一个无与伦比的研究平台，用于研究灵长类动物正常和不同状态下的大脑功能 具有高人类转化价值的疾病状态。