The sacral autonomic outflow is sympathetic

The autonomic nervous system regulates the function of internal organs such as the gut. The parasympathetic and sympathetic arms of this system tend to operate antagonistically. Espinosa-Medina et al. used anatomical and molecular analyses to reevaluate the assignment of neurons in the sacral autonomic nervous system (see the Perspective by Adameyko). Previously categorized as parasympathetic, these neurons are now identified as sympathetic. The results resolve a persistent confusion about how the two systems developed and open the avenue to more predictable outcomes in developing treatments targeted to the pelvic autonomic nervous system. Science, this issue p. 893; see also p. 833 Contrary to a century-old dogma, the pelvic nerves and ganglia do not belong to the parasympathetic nervous system but to the sympathetic one. A kinship between cranial and pelvic visceral nerves of vertebrates has been accepted for a century. Accordingly, sacral preganglionic neurons are considered parasympathetic, as are their targets in the pelvic ganglia that prominently control rectal, bladder, and genital functions. Here, we uncover 15 phenotypic and ontogenetic features that distinguish pre- and postganglionic neurons of the cranial parasympathetic outflow from those of the thoracolumbar sympathetic outflow in mice. By every single one, the sacral outflow is indistinguishable from the thoracolumbar outflow. Thus, the parasympathetic nervous system receives input from cranial nerves exclusively and the sympathetic nervous system from spinal nerves, thoracic to sacral inclusively. This simplified, bipartite architecture offers a new framework to understand pelvic neurophysiology as well as development and evolution of the autonomic nervous system.