Stressor-Selective Sympathetic Preganglionic Modules for Organ-Biased Control

Abstract

The sympathetic nervous system coordinates organ function during stress, yet the spinal organization that converts autonomic commands into selective peripheral outputs remains poorly understood. Here, we combined spatial transcriptomics, immediate early gene mapping, anatomical tracing, and functional perturbation to define the cellular logic of spinal sympathetic preganglionic neurons (SPNs) in mice. SPN transcriptomic subtypes were spatially organized by spinal segment and sex and recruited in distinct combinations by physiological stressors, revealing stressor-selective sympathetic output modules. Focusing on cold-responsive neurotensin-expressing (Nts+) SPNs in the lower thoracic spinal cord, we found that they formed a distinct output channel to the lower sympathetic trunk and aorticorenal ganglia, promoted female-biased mobilization of white adipose tissue lipids, and were required for cold tolerance when food was unavailable. These findings establish a cell-type-resolved spinal architecture that links physiological demand to organ-biased sympathetic output and identifies the preganglionic layer as a key organizer of brain-body control.