Virtual Realty Systems for Neural Circuit Dynamics

描述（由申请人提供）：本申请涉及广泛的挑战领域06：使能技术。具体的挑战主题是06-NS-103：神经科学的突破性技术。虚拟现实（VR）是允许用户与计算机模拟环境交互的技术。环境可以表示真实的世界的模拟，也可以表示可以在真实的时间中被修改以提供认知的新颖探测的想象世界。广泛用于人类行为和神经成像实验，我们现在建议将这项技术应用于啮齿动物细胞分辨率神经回路研究的不同领域。我们将开发VR仪器和软件，可以与体内双光子激光扫描显微镜和体内全细胞补丁记录协同工作，为系统神经科学提供新的功能。这项技术围绕着头部受限的啮齿动物在悬浮球体表面上行走和奔跑。我们最近已经证明，这种球形跑步机可以使用双光子激光扫描显微镜，以提供测量钙瞬变的细胞分辨率从人口（~100）的皮层神经元在清醒的，移动的，小鼠。为了增加视觉VR功能，一个跨越啮齿动物视野的环形屏幕围绕着球。该屏幕显示投影的计算机生成的图像，该图像已被几何变换以提供从鼠标的视角的虚拟环境的真实图像。检测由受试者的运动产生的球的运动的传感器向计算机提供控制信号，用于在环境内的转向和向前运动。最近完成的试点实验，使用该装置表明，小鼠，在一个仪器条件反射范例，学习导航虚拟竞技场和迷宫的水奖励。单个单元的录音演示了虚拟环境中的位置细胞。此外，该系统提供了在导航过程中应用体内全细胞细胞内记录方法的能力，并证明了位置细胞的第一次细胞内记录。通过结合VR与双光子成像，在导航过程中监测海马锥体细胞群的能力也得到了证明。基于这些结果，一组在神经科学不同领域工作的研究人员将共同努力，扩大啮齿动物VR系统的开发，作为一项新的突破性技术。首先，我们将根据第一代系统的经验，开发改进的显示器，球形研磨机，运动传感器和视觉VR软件。这将提高现有视觉VR系统的整体性能，并使其易于被更广泛的神经科学界采用。将构建用于表征位置细胞和网格细胞的VR环境，并将这些细胞的特性与在真实的环境中观察到的特性进行比较。第二，我们将开发一个球形跑步机和相关仪器的头部限制大鼠VR，一个物种广泛用于研究的导航，最近，执行控制。第三，我们将开发仪器，以增加新的感觉方式和反馈能力。将开发VR控制的嗅觉和听觉刺激。为了研究小脑在运动控制中的作用，将开发一种计算机控制的阻力跑步机，提供实时的本体感受反馈。在所有情况下，VR仪器将被优化用于体内双光子激光扫描显微镜和全细胞细胞内补丁记录。完成后，这套新仪器将为系统神经科学界提供新的功能，用于清醒行为啮齿动物电路的细胞分析。这项研究将开发用于神经科学研究的虚拟现实系统。该系统将能够在受试者在虚拟环境中导航时测量大脑中一个或多个单个神经元中的电和化学过程。这种能力在比较大脑的正常状态和疾病状态方面很有价值。开发的方法将适用于小鼠，这是健康研究中领先的哺乳动物遗传模型。它也将为大鼠开发，这是一种广泛用于行为研究的物种。

Description (provided by applicant): This application addresses broad Challenge Area 06: Enabling Technologies. The specific Challenge Topic is 06-NS-103: Breakthrough Technologies in Neuroscience. Virtual reality (VR) is a technology that allows a user to interact with a computer- simulated environment. The environment can represent a simulation of the real world or an imaginary world that can be modified in real time to provide a novel probe of cognition. Widely used in human behavior and neuro-imaging experiments, we now propose to bring this technology to bear on diverse areas in the study of neural circuits at cellular resolution in rodents. We will develop VR instrumentation and software that can work in a synergistic way with both in vivo two photon laser scanning microscopy and in vivo whole cell patch recording to provide new capabilities in systems neuroscience. The technology revolves around the use of head-restrained rodents walking and running on the surface of a levitated sphere. We have recently demonstrated that this spherical treadmill can be used with two-photon laser scanning microscopy to provide measurements of calcium transients at cellular resolution from populations (~100) of cortical neurons in awake, mobile, mice. To add visual VR capability, a toroidal screen that spans the rodent visual field surrounds the ball. This screen displays a projected computer generated image that has been geometrically transformed to provide a realistic image of the virtual environment from the mouse's perspective. Sensors that detect the motion of the ball produced by movements of the subject provide a control signal to a computer for both turning and forward motion within the environment. Recently completed pilot experiments using this apparatus demonstrate that mice, in an instrumental conditioning paradigm, learn to navigate in virtual arenas and mazes for water rewards. Single unit recordings demonstrate place cells in the virtual environments. Furthermore, the system provides the capability to apply in vivo whole cell intracellular recording methods during navigation and the first intracellular recordings of place cells are demonstrated. By combining VR with two-photon imaging, the capability for monitoring populations of hippocampal pyramidal cells during navigation is also demonstrated. Based on these results, a team of investigators working in diverse areas of neuroscience will work together to expand the development of VR systems for rodents as a new breakthrough technology. First, we will develop improved displays, spherical treadmills, motion sensors, and visual VR software based on experience with the first generation system. This will improve the performance of the existing visual VR system in general and also allow it to be easily adopted by the wider neuroscience community. VR environments for the characterization of place cells and grid cells will be constructed and the characteristics of these cells will be compared to that observed in real environments. Second, we will develop a spherical treadmill and associated instrumentation for head restrained rat VR, a species widely used in studies of navigation and, more recently, executive control. Third, we will develop instrumentation for adding new sensory modalities and feedback capabilities. VR-controlled olfactory and auditory stimuli will be developed. For studies of the role of the cerebellum in motor control, a computer-controlled resistance treadmill will be developed that provides proprioceptive feedback in real-time. In all cases, the VR instrumentation will be optimized for use with in vivo two-photon laser scanning microscopy and whole cell intracellular patch recording. When completed, the suite of new instrumentation will provide the systems neuroscience community with new capabilities for cellular analysis of circuits in awake behaving rodents. This study will develop virtual reality systems for use in neuroscience research. The system will enable the measure of electrical and chemical processes in one or many individual neurons in the brain while the subject is navigating in a virtual environment. This capability would be valuable in comparing normal and diseased states in the brain. The methods developed will be applicable to the mouse, which is the leading mammalian genetic model in health research. It will also be developed for the rat, a species widely used in behavioral studies.