Rethinking the autonomic nervous system: genetics and cell fate


Frances Lefcort


Clinical Autonomic Research


Gaskell and Langley’s classical studies from the nineteenth and twentieth century described the autonomic nervous system (ANS) outflow as being divided into three neuraxial regions: a thoraco-lumbar sympathetic circuit bracketed by cranial, brainstem parasympathetic and sacral parasympathetic circuits. These and subsequent anatomical, physiological and pharmacological studies formed the foundational basis for our organizational understanding of the ANS with preganglionic neurons in the brainstem and sacral cord innervating parasympathetic postganglionic neurons that were in close proximity to their targets, while thoraco-lumbar preganglionic neurons innervated paravertebral and pre-vertebral sympathetic ganglia that tended to be further away from their target organs. Jean-Francois Brunet and colleagues challenged this classification schema in 2016 [1] with the surprising finding that neurons in the “sacral parasympathetic” outflow circuit express 15 different phenotypic and ontogenetic features of pre- and postganglionic sympathetic neurons, rather than of pre- and postganglionic parasympathetic neurons. These genetic and developmental data argue against a distinction in phenotype between thoracic and sacral spinal preganglionic neurons, and rather indicate that the entire spinal ANS outflow—from thoracic to sacral—is sympathetic, while only the cranial brainstem output is parasympathetic.



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