Novel freely moving monkey framework for the study of naturalistic behaviors

项目总结/摘要 动物生活在动态的、不断变化的环境中。因此，生存需要他们探索自己的 环境和处理一连串的感官信号，以形成关于预期和如何预测的预测。 对传入的感官信息做出反应。自然主义行为所需的神经处理过程是高度复杂的。 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，为了理解神经基础， 自然的行为，同时研究动物模型的行为和神经活动是必要的 在相对不受限制的条件下。这种工作的一个典范是导航的神经基础， 啮齿动物和蝙蝠。然而，人类的认知能力，灵巧的手和面向前方的视觉系统 和非人类灵长类动物（NHP）使他们能够预测和影响他们的环境。 因此，NHP是研究复杂， 自然主义行为。因此，当前提案的目标是开发和审查一个新的研究平台， 使用导航作为模型系统，对NHP进行自然主义研究。迄今为止， 障碍已经排除了一个强大的自由移动的猴子（FMM）框架的发展。在这里，我们建议 对雌性和雄性恒河猴实施全无线行为和多通道神经元数据采集 猴子（Maccaca mulatta）在一个开放的领域FMM竞技场的自由探索。我们将使用3D运动 捕捉技术来记录头部、身体和上肢的运动。一种定制的新型面罩 并对每只动物进行个性化，将用于进行双眼眼跟踪。此外，一种新颖的微驱动器 磁共振成像兼容的系统将用于安全地同时引入 电极进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。微驱动系统和移动的神经记录仪将包含在颅骨植入物内， 使得当动物在FMM竞技场以及家庭围栏内时能够进行无系绳记录。来审查 FMM框架，我们建议使用自由觅食范例。我们将专门测试， 在啮齿动物和蝙蝠中发现的导航特性在NHP中是保守的。重要的是，我们将探讨 灵长类动物大脑中的神经回路也是精心设计的，以利用双目、面向前方的视觉系统。 特别是，我们将研究自然行为过程中神经元的凝视相关特性。我们高度 预计通过这个新的研究平台获得的行为和神经元数据将是前所未有的， 从而能够更全面地了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 该框架将成为一个无与伦比的研究平台，用于研究正常和 具有高人类转化价值的疾病状态。

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.