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.
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一种基因编码工具,用于重建合成调节神经传递并重新连接体内神经回路。

DOI:
10.1038/s41467-021-24690-9
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发表时间:
2021-08-09
影响因子:
16.6
通讯作者:
Colón-Ramos DA
Colón-Ramos DA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hawk JD;Wisdom EM;Sengupta T;Kashlan ZD;Colón-Ramos DA

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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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