HySyn: A genetically-encoded synthetic synapse to rewire neural circuits in vivo

Here we introduce HySyn, a system designed to rewire neural connectivity by reconstituting a functional heterologous synapse. We demonstrate that genetically targeted expression of the two HySyn components, a -derived neuropeptide and its receptor, creates neuromodulatory transmission in a mammalian neuronal tissue culture model and rewires a behavioral circuit in the nematode . HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or modulate specific neural circuits.