3D Printed Multifunctional Brain Windows for Simultaneous Optical Imaging and Electrophysiology

项目摘要 本提案响应了PAR-18 - 870，标题为"BRAIN倡议：开发优化和验证 神经科学研究的新工具和技术（STTR）。该项目是一个快速通道STTR， 第一阶段和第二阶段小企业，应用通用动力公司（AUD）正在与 明尼苏达大学（明尼苏达大学）。数以千万计的神经元的活动模式--都组织成回路 分布在多个大脑区域，调节我们与外界的互动。一种机械的 理解感官知觉、动作、情感和认知的神经元基础需要 测量这些神经元回路的活动，在单个细胞分辨率跨越几毫米，并在多个 时间尺度时间尺度我们建议设计和商业推广透明聚合物 同时允许宽视野光学神经感测沿着高时间分辨率电 整个哺乳动物皮层的记录。我们将在我们实验室开发的关键技术的基础上继续发展。 具体来说，我们的合作已经开发出一种方法来设计和制造透明的头骨（大脑 窗口），允许亚细胞分辨率成像的结构和功能的整个背皮层， 行为老鼠在本提案的第一阶段，我们将首先利用三维打印方法， 用8个通道的透明皮层电图（ECoG）记录功能化这些透明头骨 电极（目标1）。这些设备将用于同时进行中尺度钙成像， ECoG记录（Aim 2）。在本提案的第二阶段，我们将完善3D打印方法， 超高密度，透明的128通道ECOG阵列（目标1），用于同时进行整个皮层ECoG和 细胞分辨率钙显像（Aim 2）。最后，我们将设计新的技术版本， 利用表面ECoG和整个皮层光学成像同时进行细胞外记录，以实现平台 这允许真正的3D大脑活动映射（Aim 3）。

PROJECT SUMMARY This proposal responds to PAR-18-870 titled “BRAIN Initiative: Development Optimization, and Validation of Novel Tools and Technologies for Neuroscience Research (STTR).” This project is a Fast Track STTR with a phase I and phase II. The small business, Applied Universal Dynamics Corp. (AUD) is collaborating with the University of Minnesota (U of MN). The activity patterns of tens of millions of neurons – all organized into circuits distributed across multiple brain regions mediate our interaction with the outside world. A mechanistic understanding of the neuronal underpinnings of sensory perception, action, emotion, and cognition requires measuring activities of these neuronal circuits at single cell resolution across several millimeters, and at multiple temporal scales temporal scales. We propose to engineer and commercially disseminate transparent polymer skulls that simultaneously allow wide-field optical neural sensing along with high temporal resolution electrical recordings from the whole mammalian cortex. We will build on key technologies developed in in our laboratories. Specifically, our collaborative has developed a methodology to design and fabricate transparent skulls (Brain Windows) that allow sub-cellular resolution imaging of structure and function of the whole dorsal cortex in behaving mice. In PHASE I of this proposal, we will first utilize 3-dimensional printing methodologies to functionalize these transparent skulls with 8 channels of transparent electrocorticogram (ECoG) recording electrodes (Aim 1). These devices will be utilized to perform simultaneous mesoscale calcium imaging and ECoG recordings (Aim 2). In PHASE II of this proposal, we will refine the 3D printing methodology to realize ultra-high density, transparent 128 channel ECoG arrays (Aim 1) for simultaneous whole cortex ECoG and cellular resolution calcium imaging (Aim 2). Finally, we will engineer versions of the technology that allow simultaneous extracellular recordings with surface ECoG and whole cortex optical imaging to realize a platform that allows true 3D brain activity mapping (Aim 3).