Novel freely moving monkey framework for the study of naturalistic behaviors

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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.