bioRxiv preprint doi: https://doi.org/10.1101/2021.05.05.442702; this version posted May 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Mapping the Central and Peripheral Projections of Lung Innervating Sensory Neurons Yujuan Su1*, Justinn Barr1*, Abigail Jaquish1, Jinhao Xu1, Jamie M Verheyden1, Xin Sun1,2, # Affiliations 1Department of Pediatrics, University of California, San Diego, CA 92093, USA. 2Division of Biological Sciences, University of California, San Diego, CA 92093, USA. *These authors contribute equally to this work. #Corresponding author:
[email protected]. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.05.442702; this version posted May 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract While best known as the gas exchange organ, the lung is also critical for sensing and responding to the aerosol environment in part through interaction with the nervous system. The rich diversity of lung innervating neurons remains poorly understood. Here, we interrogated the cell body location, projection pattern and targets of lung-innervating sensory neurons. Retrograde tracing from the lung labeled neurons primarily in the vagal ganglia, in a spatially distributed population expressing markers including Vglut2, Trpv1, Tac1, Calb1 or Piezo2. Centrally, they project to the nucleus of the solitary tract in the brainstem. Peripherally, they project along the branching airways and terminate on airway smooth muscles, vasculature including lymphatics, and selected alveoli.