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

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

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 dev...

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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; p. 4795
Main Authors: Hawk, Josh D., Wisdom, Elias M., Sengupta, Titas, Kashlan, Zane D., Colón-Ramos, Daniel A.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 09-08-2021
Nature Publishing Group
Nature Portfolio
Subjects:
14/35
14/63
631/378/3920
631/378/548
64/11
Calcium (intracellular)
Calcium ions
Circuit design
Circuits
Genetic code
Genetic engineering
Humanities and Social Sciences
multidisciplinary
Nematodes
Nervous system
Neural networks
Neuropeptides
Neurotransmission
Rewiring
Science
Science (multidisciplinary)
Synaptic transmission
Tissue culture
Worms
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Summary: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. Engineering de novo synapse-like connections between neurons could enhance our understanding of neuronal circuits and how they generate behaviour. The authors present a two-component system that creates synthetic neuromodulatory connections to manipulate intracellular Ca2+ levels in in vivo neural circuits.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24690-9