Cellular, Molecular and Developmental NeuroscienceGlycine as a signaling molecule and chemoattractant in Trichoplax (Placozoa): insights into the early evolution of neurotransmittersRomanova, Daria Y.a,,b,,*; Heyland, Andreasc,,*; Sohn, Dosungd,,*; Kohn, Andrea B.d; Fasshauer, Dirka; Varoqueaux, Frederiquea; Moroz, Leonid L.d,,e Author Information aDepartment of Fundamental Neuroscience, University of Lausanne, Lausanne, Switzerland bInstitute of Higher Nervous Activity and Neurophysiology, Moscow, Russia cDepartment of Integrative Biology, University of Guelph, Guelph, Ontario, Canada dWhitney Laboratory for Marine Biosciences, University of Florida, St. Augustine eDepartments of Neuroscience and McKnight Brain Institute, University of Florida, Gainesville, Florida, USA *Daria Y. Romanova, Andreas Heyland and Dosung Sohn contributed equally to the writing of this article. Received 27 January 2020 Accepted 20 February 2020 Correspondence to Leonid L. Moroz, PhD, Department of Neuroscience, Whitney Laboratory, College of Medicine, 9505 Ocean Shore Blvd., St. Augustine, FL 32080, USA, Tel: +1 904 461 4000; email: [email protected] NeuroReport: April 8, 2020 - Volume 31 - Issue 6 - p 490-497 doi: 10.1097/WNR.0000000000001436 Buy Metrics Abstract The origin and early evolution of neurotransmitter signaling in animals are unclear due to limited comparative information, primarily about prebilaterian animals. Here, we performed the comparative survey of signal molecules in placozoans – the simplest known free-living animals without canonical synapses, but with complex behaviors. First, using capillary electrophoresis with laser-induced fluorescence detection, we performed microchemical analyses of transmitter candidates in Trichoplax adhaerens – the classical reference species in comparative biology. We showed that the endogenous level of glycine (about 3 mM) was significantly higher than for other candidates such as L-glutamate, L-aspartate, or gamma-aminobutyric acid. Neither serotonin nor dopamine were detected. The absolute glycine concentrations in Trichoplax were even higher than we measured in ctenophores (Beroe) and cnidarians (Aequorea). We found that at millimolar concentrations of glycine (similar to the endogenous level), induced muscle-like contractions in free behaving animals. But after long incubation (24 h), 10−3 M of glycine could induce cytotoxicity and cell dissociation. In contrast, micromolar concentrations (10−5–10−4 M) increased Trichoplax ciliated locomotion, suggesting that glycine might act as an endogenous signal molecule. However, we showed than glycine (10−6 M) can also be a chemoattractant (a guiding factor for food sources), and therefore, act as the exogenous signal. These findings provide an evolutionary base for the origin of transmitters as a result of the interplay between exogenous and endogenous signaling systems early in animal evolution. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.