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

 描述（由申请人提供）：随着光遗传学工具的持续扩展，神经活动的光学测量的核心重要性已经并将继续增长。 然而，大规模的光学方法，如脑倡议所追求的，必须克服脑组织中的高光散射。 此外，光学方法在行为动物中应该是可行的，包括自由移动的小鼠。 我们将开发一种超微型显微内窥镜，称为针式光极，由一个裸露的光纤束倾斜到一个很好的尖端。 与现有技术相比，更小的尺寸和斜切改善了组织穿透并降低了组织损伤，并且布置了用于跨分层结构（诸如新皮层）成像的视场。 该项目的核心贡献是通过无透镜设计实现小型化，使用阵列检测器的创新耦合，以实现荧光背景抑制和远程聚焦。 我们将展示我们的方法收集大规模的，多区域的数据，同时记录从对齐的皮层和丘脑区域的小鼠体感系统，在麻醉小鼠的权力。 这些目标的完成将使我们能够同时记录整个丘脑皮层触须处理网络，包括前馈和反馈预测，并成为在清醒的动物中执行这些记录的第一步，这些记录积极参与触觉任务中感兴趣的对象。 此外，我们的方法-提供多区域，细胞分辨率记录 基因识别的细胞类型，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BRAIN计划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.