Prebilaterian origin of monoaminergic signaling

Monoamines such as serotonin, dopamine, and tyramine regulate physiological and behavioral processes in bilaterian animals, but the evolutionary origin of the monoaminergic system remains unclear. Placozoans are non-bilaterian, neuronless animals with coordinated behaviors, making them a key group for testing the evolutionary origin of this system. Here, we combined receptor deorphanization, phylogenetics, and behavioral assays to test whether monoaminergic signaling operates in the placozoan Trichoplax adhaerens. We identified five receptors activated by tyramine, tryptamine, or phenethylamine, four of which are homologous to bilaterian melatonin receptors, revealing an evolutionary link between placozoan and bilaterian monoamine receptors. Using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), we detected these monoamines endogenously, and heterologous complementation demonstrated that the placozoan amino acid decarboxylase (AADC) enzyme can support tyramine production in vivo. Behavioral assays showed that tyramine increased locomotion speed, whereas tryptamine induced body contractions and shape changes in T. adhaerens. These findings provide evidence of an active monoaminergic signaling system in placozoans and support that core components of monoamine synthesis and detection were already present before bilaterian diversification.