Novel freely moving monkey framework for the study of naturalistic behaviors

项目摘要/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 并处理接二连三的感官信号，以形成对预期和如何预期的预测 对传入的感官信息做出反应。自然主义行为所必需的神经处理是高度的 复杂的，需要多种大脑功能的协调，包括多感觉处理、感觉运动 整合、认知功能、运动计划和执行。因此，要了解神经基础 自然行为，必须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。这项工作的一个典型例子是导航的神经基础 啮齿动物和蝙蝠。然而，人类的认知能力、灵巧的手和前视系统 非人灵长类使它们具有独特的预测和影响环境的能力。 因此，NHPS是研究复杂脑功能的理想动物模型， 自然主义的行为。因此，当前提案的目标是开发和审查一个新的研究平台 以航海为模式系统，与国家海洋生物研究所进行自然主义研究。到目前为止，重大的技术 障碍阻碍了健壮的自由活动猴子(FMM)框架的开发。在这里，我们建议 雌性和雄性恒河猴实现全无线行为和多通道神经元数据采集 猴子(Maccaca Mulatta)在自由探索开阔的FMM竞技场。我们将使用3D动画 捕捉技术可以记录头部、身体和上肢的运动。一种定制设计的新型口罩 并针对每只动物进行个性化的双目眼睛跟踪。此外，一种新型的微驱动器 与磁共振成像兼容的系统将用于安全和同时地引入 电极进入边缘系统的多个深部大脑区域，以及精确地验证记录位置 没有组织学。微驱动系统和移动神经记录仪将被包含在颅骨植入物中， 当动物在FMM竞技场和家庭围栏内时，可以进行无系绳录制。审阅 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已经建立了 在啮齿动物和蝙蝠身上发现的导航特性在NHP中是保守的。重要的是，我们将探索 灵长类动物大脑中的神经回路也被详细阐述，以利用双目的前视系统。 特别是，我们将研究神经元在自然行为中与凝视相关的特性。我们高度重视 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， 使人们能够更全面地了解自然主义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，这项提议为FMM奠定了基础 框架将成为无与伦比的研究平台，用于研究正常和 疾病状态具有很高的人类翻译价值。

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.