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

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2021-08-09Author
Hawk, Josh D.
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Wisdom, Elias M.
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Sengupta, Titas
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Kashlan, Zane D.
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Colón-Ramos, Daniel
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https://hdl.handle.net/1912/27698As published
https://doi.org/10.1038/s41467-021-24690-9DOI
10.1038/s41467-021-24690-9Abstract
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.
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© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hawk, J. D., Wisdom, E. M., Sengupta, T., Kashlan, Z. D., & Colon-Ramos, D. A. A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo. Nature Communications, 12(1), (2021): 4795, https://doi.org/10.1038/s41467-021-24690-9.
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Hawk, J. D., Wisdom, E. M., Sengupta, T., Kashlan, Z. D., & Colon-Ramos, D. A. (2021). A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo. Nature Communications, 12(1), 4795.The following license files are associated with this item: