PT - JOURNAL ARTICLE AU - Josh D. Hawk AU - Daniel A. Colón-Ramos TI - HySyn: A genetically-encoded synthetic synapse to rewire neural circuits <em>in vivo</em> AID - 10.1101/2020.01.27.922203 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.27.922203 4099 - http://biorxiv.org/content/early/2020/01/28/2020.01.27.922203.short 4100 - http://biorxiv.org/content/early/2020/01/28/2020.01.27.922203.full AB - Here we introduce HySyn, a system designed to rewire neural connectivity in vivo by reconstituting a functional heterologous synapse. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or modulate specific neural circuits.