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Neurogastroenterol Motil. 2018 Feb;30(2). doi: 10.1111/nmo.13234. Epub 2017 Oct 11.

The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems.

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Florey Institute of Neuroscience and Mental Health, Parkville, Vic, Australia.
Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Vic, Australia.



The enteric nervous system (ENS) and the central nervous system (CNS) of mammals both contain integrative neural circuitry and similarities between them have led to the ENS being described as the brain in the gut.


To explore relationships between the ENS and CNS across the animal kingdom. We found that an ENS occurs in all animals investigated, including hydra, echinoderms and hemichordates that do not have a CNS. The general form of the ENS, which consists of plexuses of neurons intrinsic to the gut wall and an innervation that controls muscle movements, is similar in species as varied and as far apart as hydra, sea cucumbers, annelid worms, octopus and humans. Moreover, neurochemical similarities across phyla imply a common origin of the ENS. Investigation of extant species suggests that the ENS developed in animals that preceded the division that led to cnidaria (exemplified by hydra) and bilateria, which includes the vertebrates. The CNS is deduced to be a bilaterian development, later than the divergence from cnidaria. Consistent with the ENS having developed independent of the CNS, reciprocal connections between ENS and CNS occur in mammals, and separate neurons of ENS and CNS origin converge on visceral organs and prevertebral ganglia. We conclude that an ENS arose before and independently of the CNS. Thus the ENS can be regarded as the first brain.


central nervous system; enteric nervous system; evolution; neurotransmitters; serotonin


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