A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo

Josh D. Hawk (), Elias M. Wisdom, Titas Sengupta, Zane D. Kashlan and Daniel A. Colón-Ramos ()
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Josh D. Hawk: Grass Laboratory, Marine Biological Laboratory
Elias M. Wisdom: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine
Titas Sengupta: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine
Zane D. Kashlan: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine
Daniel A. Colón-Ramos: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Chemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. 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 functionally 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 achieve targeted modulation of specific neural circuits and behaviors.

Date: 2021
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DOI: 10.1038/s41467-021-24690-9

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