FlatScopes for Implantable and Scalable Optical Imaging of Neural Activity

项目总结： 对完整动物个体神经元活动的大规模测量将加速对 大脑和神经疾病的治疗。幸运的是，过去十年见证了戏剧性的 基于新的基因编码的钙-OR记录神经活动的光学方法的改进 电压依赖的荧光蛋白。这些光学技术有可能记录来自 数以千计的神经元具有单细胞分辨率，因为细胞活动可以从 没有植入会损害神经组织的大脑。 不幸的是，目前用于自由活动动物的荧光显微镜工具不能 由于显微镜尺寸大，视野小，一次记录的细胞超过几百个 查看(FOV)。为了实现对哺乳动物中数千个单个神经元的同时成像，荧光 显微镜必须小型化和排列，这样动物才能自由地与环境互动 而神经活动的图像则持续记录在大脑的大片区域。 我们的工作目标是创造一种新的平板显微镜(每一种都有一个大的视场)，可以排列和放置在上面 自由活动动物的大脑。这些显微镜阵列因此将在大范围内提供连续成像 在自由活动的动物中具有细胞分辨率的大脑。我们还设想，这些平面镜可以植入 进入大脑，以测量太深而无法从表面成像的区域的神经活动。 为了创建这些平面镜，我们将利用来自现场计算成像的新兴技术，这 使现在有可能用紧凑型显微镜取代昂贵、笨重和厚重的镜片， 重量轻，价格低廉的衍射掩模放置在传感器附近。然后，可以使用以下命令重建图像 从多路传输的传感器测量中恢复荧光图像的算法。我们的PI团队 具备计算成像、纳米级神经接口和活体神经数据采集方面的专业知识将会发挥作用 将无透镜成像的想法转化为可植入的微型平面显微镜，可以成像大脑中的神经活动 自由活动的动物。 我们与R21基金的目标是设计、制造和表征个人可植入平面镜，无论是在 为可扩展的成像技术测量钙-或电压-奠定了基础 数千个神经元中具有单一细胞分辨率的敏感荧光。

Project Summary: Large-scale measurement of individual neuronal activity in intact animals will accelerate the understanding of the brain and treatment of neurological disorders. Fortunately, the last decade has witnessed dramatic improvements in optical methods to record neural activity based on new genetically encoded calcium- or voltage-dependent fluorescence proteins. These optical techniques have the potential to record activity from many thousands of neurons with single-cell resolution because cell activity can be imaged from the surface of the brain without implants that damage neural tissue. Unfortunately, the current tools for fluorescence microscopy in freely moving animals are incapable of recording from more than a few hundred cells at a time due to the large microscope size and small field of view (FOV). To achieve simultaneous imaging of thousands of individual neurons in mammals, fluorescence microscopes must be miniaturized and arrayed so that animals can freely interact with their environment while images of neural activity are constantly recorded over large areas of brain. The goal of our work is to create a new class of flat microscopes (each with a large FOV) that can be arrayed and placed on the brain of a free-moving animal. These microscope arrays will thereby provide continuous imaging over large areas of the brain with cellular resolution in freely moving animals. We also envision that these FlatScopes could be implanted into the brain to measure neural activity from regions that are too deep to image from the surface. To create these FlatScopes we will exploit emerging technologies from the field computational imaging, which make it now possible to replace the expensive, heavy and thick lenses in microscopes with a compact, lightweight, and inexpensive diffractive mask placed near the sensor. Images can then be reconstructed using algorithms that recover the fluorescence images from the multiplexed sensor measurements. Our team of PIs with expertise in computational imaging, nanofabricated neural interfaces, and in vivo neural data acquisition will work to translate the ideas of lens-free imaging to implantable microfabricated FlatScopes that can image neural activity in freely moving animals. Our goal with R21 funding is to design, fabricate, and characterize individual implantable FlatScopes, both in vitro and in vivo, laying the groundwork for a scalable imaging technology to measure calcium- or voltage- sensitive fluorescence in thousands of neurons with single cell resolution.