RT Journal Article SR Electronic T1 The origin and evolution of acetylcholine signaling through AchRs in metazoans JF bioRxiv FD Cold Spring Harbor Laboratory SP 424804 DO 10.1101/424804 A1 Faltine-Gonzalez, Dylan Z. A1 Layden, Michael J YR 2018 UL http://biorxiv.org/content/early/2018/09/23/424804.abstract AB Background Acetylcholine is a cell signaling molecule that has been identified in plants, bacteria, and metazoans to play multiple roles in cells and as a neurotransmitter capable of exciting both neurons and muscle. While cell-cell communication activity has been reported in all phyla that have been investigated, its role as a neurotransmitter is less clear. Work within cnidarians implies that neurotransmitter activity emerged within or prior to the emergence of the cnidarian-bilaterian ancestor, but whether or not it is able to excite both muscles and neurons has not been addressed.Results To investigate the evolution of acetylcholine signaling we characterized the expression pattern of acetylcholine receptors (AchRs) and the neurotransmitter activity of acetylcholine in Nematostella vectensis. Expression patterns for 13 of the 21 known NvAchRs are consistent with acetylcholine acting as a cell signaling molecule and a neurotransmitter in neurons, muscles, or both. To dissect neurotransmitter activity we investigated the mechanism by which acetylcholine activates tentacular contractions in Nematostella. Tentacular contractions induced by application of acetylcholine are suppressed by inactivating voltage gated sodium channels with lidocaine indicating that acetylcholine specifically activates neurons in the tentacular contractile circuit.Conclusion Our results verify that acetylcholine’s neurotransmitter activity emerged prior to cnidarian-bilaterian divergence and that non-neuronal roles were likely retained in Nematostella. Additionally, we found no evidence to support a muscle activating role for acetylcholine indicating that its role in muscle excitability evolved during bilaterian evolution.nAchRnicotinic acetylcholine receptormAchRmuscarinic acetylcholine receptorhpfhours post fertilization