Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States of America.
Duke Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, United States of America.
J Neural Eng. 2021 Jun 8;18(4). doi: 10.1088/1741-2552/ac0089.
The peripheral nervous system (PNS) connects the central nervous system with the rest of the body to regulate many physiological functions and is therapeutically targeted to treat diseases such as epilepsy, depression, intestinal dysmotility, chronic pain, and more. However, we still lack understanding of PNS innervation in most organs because the large span, diffuse nature, and small terminal nerve bundle fibers have precluded whole-organism, high resolution mapping of the PNS. We sought to produce a comprehensive peripheral nerve atlas for use in future interrogation of neural circuitry and selection of targets for neuromodulation.We used diffusion tensor magnetic resonance imaging (DT-MRI) with high-speed compressed sensing to generate a tractogram of the whole mouse PNS. The tractography generated from the DT-MRI data is validated using lightsheet microscopy on optically cleared, antibody stained tissue.Herein we demonstrate the first comprehensive PNS tractography in a whole mouse. Using this technique, we scanned the whole mouse in 28 h and mapped PNS innervation and fiber network in multiple organs including heart, lung, liver, kidneys, stomach, intestines, and bladder at 70m resolution. This whole-body PNS tractography map has provided unparalleled information; for example, it delineates the innervation along the gastrointestinal tract by multiple sacral levels and by the vagal nerves. The map enabled a quantitative tractogram that revealed relative innervation of the major organs by each vertebral foramen as well as the vagus nerve.This novel high-resolution nerve atlas provides a potential roadmap for future neuromodulation therapies and other investigations into the neural circuits which drive homeostasis and disease throughout the body.
周围神经系统（PNS）连接中枢神经系统与身体的其余部分，以调节许多生理功能，并被用于治疗癫痫、抑郁、肠道动力障碍、慢性疼痛等疾病。然而，由于大范围、弥散性和小末梢神经束纤维的存在，我们仍然缺乏对大多数器官的 PNS 支配的了解，这使得我们无法对整个器官的 PNS 进行高分辨率的映射。我们试图制作一个全面的周围神经图谱，用于未来对神经回路的研究和对神经调节的靶点选择。
我们使用弥散张量磁共振成像（DT-MRI）结合高速压缩感知来生成整个小鼠 PNS 的轨迹图。通过对经过光学透明处理和抗体染色的组织进行光片显微镜检查，对从 DT-MRI 数据生成的轨迹图进行验证。
在这里，我们展示了首个在整个小鼠中进行的全面 PNS 轨迹图。使用这项技术，我们在 28 小时内扫描了整个小鼠，并以 70 微米的分辨率绘制了多个器官（包括心脏、肺、肝、肾、胃、肠和膀胱）的 PNS 支配和纤维网络。这个全身 PNS 轨迹图提供了无与伦比的信息；例如，它描绘了多个骶骨水平和迷走神经沿胃肠道的支配。该图谱还能够进行定量轨迹图分析，揭示每个椎间孔和迷走神经对主要器官的相对支配。
这项新的高分辨率神经图谱为未来的神经调节治疗和对全身驱动稳态和疾病的神经回路的其他研究提供了潜在的路线图。
