A lack of comprehensive mapping of ganglionic inputs into the pancreas and of technology for the modulation of the activity of specific pancreatic nerves has hindered the study of how they regulate metabolic processes. Here we show that the pancreas-innervating neurons in sympathetic, parasympathetic and sensory ganglia can be mapped in detail by using tissue clearing and retrograde tracing (the tracing of neural connections from the synapse to the cell body), and that genetic payloads can be delivered via intrapancreatic injection to target sites in efferent pancreatic nerves in live mice through optimized adeno-associated viruses and neural-tissue-specific promoters. We also show that, in male mice, the targeted activation of parasympathetic cholinergic intrapancreatic ganglia and neurons doubled plasma-insulin levels and improved glucose tolerance, and that tolerance was impaired by stimulating pancreas-projecting sympathetic neurons. The ability to map the peripheral ganglia innervating the pancreas and to deliver transgenes to specific pancreas-projecting neurons will facilitate the examination of ganglionic inputs and the study of the roles of pancreatic efferent innervation in glucose metabolism.

由于缺乏对胰腺神经节输入的全面定位以及调节特定胰腺神经活动的技术，阻碍了对它们如何调节代谢过程的研究。在这里，我们展示了通过使用组织清除和逆行追踪（追踪从突触到细胞体的神经连接）可以详细绘制交感神经节、副交感神经节和感觉神经节中的胰腺神经元，并且可以传递遗传有效负载通过优化的腺相关病毒和神经组织特异性启动子，将其胰内注射到活体小鼠传出胰神经的靶位点。我们还发现，在雄性小鼠中，靶向激活胰内副交感胆碱能神经节和神经元使血浆胰岛素水平加倍并改善葡萄糖耐量，而刺激胰腺投射交感神经元会损害耐量。绘制支配胰腺的外周神经节并将转基因传递到特定的胰腺投射神经元的能力将有助于检查神经节输入和研究胰腺传出神经支配在葡萄糖代谢中的作用。