Multi-region, extended-depth imaging of neural activity via a novel needle microendoscope

 描述(申请人提供)：随着光遗传学工具的不断扩展，光学测量神经活动的核心重要性已经并将继续增长。然而，大规模的光学方法，如大脑倡议所追求的，必须克服脑组织中的高度光散射。此外，光学方法在动物行为上应该是可行的，包括自由移动的老鼠。我们将开发一种被称为针状光学电极的超微型显微内窥镜，它是由一根裸露的纤维束倒角到一个精细的尖端制成的。与现有技术相比，较小的尺寸和倒角改善了组织穿透性，降低了组织损伤，并安排了跨新皮质等分层结构进行成像的视野。核心项目的贡献是通过无透镜设计实现小型化，使用阵列探测器的创新耦合来实现荧光背景抑制和远程聚焦。我们将展示我们的方法在收集大规模、多区域数据方面的威力，通过在麻醉小鼠中同时记录小鼠躯体感觉系统的对准皮质和丘脑区域。完成这些目标将使我们准备好在整个丘脑皮质胡须处理网络中同时进行记录，包括前馈和反馈投影，并成为在清醒的动物中积极参与触觉任务的感兴趣对象进行这些记录的第一步。此外，我们的方法-提供多区域、细胞分辨率记录 通过基因识别的细胞类型，并可能扩展到行为动物-将支持跨大脑区域和系统的类似实验，作为大脑倡议的高优先级组成部分之一。

 DESCRIPTION (provided by applicant): With the continuing expansion of optogenetic tools, the central importance of optical measurement of neural activity has and will continue to grow. However, large scale optical approaches, such as pursued by the BRAIN Initiative, must overcome high light scattering in brain tissue. Moreover, optical approaches should be feasible in behaving animals, including freely moving mice. We will develop an ultra-miniature microendoscope, termed a needle optrode, made with a bare fiber bundle beveled to a fine tip. The smaller size and beveling improves tissue penetration and lowers tissue damage compared to existing technology, and arranges the field of view for imaging across layered structures such as neocortex. The core project contribution is achieving miniaturization through a lensless design, using an innovative coupling of array detector to enable fluorescence background rejection and remote focusing. We will demonstrate the power of our approach for collecting large scale, multiregion data by recording simultaneously from aligned cortical and thalamic regions of the mouse somatosensory system, in anesthetized mice. Completion of these aims will prepare us to record simultaneously throughout an entire thalamocortical whisker processing network, including both feedforward and feedback projections, and be a first step towards performing these recordings in an awake animal actively engaging objects of interest in a tactile task. Moreover, our approach --- providing multiregion, cellular resolution recording of genetically identified cell types, with possible extension to behaving animals --- will support similar experiments across brain regions and systems, as one of the high priority components of the BRAIN initiative.