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An optimized acetylcholine sensor for monitoring in vivo cholinergic activity

Nature methods, 2020-11, Vol.17 (11), p.1139-1146 [Peer Reviewed Journal]

COPYRIGHT 2020 Nature Publishing Group ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2020. ;ISSN: 1548-7091 ;EISSN: 1548-7105 ;DOI: 10.1038/s41592-020-0953-2 ;PMID: 32989318

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Title:
An optimized acetylcholine sensor for monitoring in vivo cholinergic activity
Author: Jing, Miao ; Li, Yuexuan ; Zeng, Jianzhi ; Huang, Pengcheng ; Skirzewski, Miguel ; Kljakic, Ornela ; Peng, Wanling ; Qian, Tongrui ; Tan, Ke ; Zou, Jing ; Trinh, Simon ; Wu, Runlong ; Zhang, Shichen ; Pan, Sunlei ; Hires, Samuel A ; Xu, Min ; Li, Haohong ; Saksida, Lisa M ; Prado, Vania F ; Bussey, Timothy J ; Prado, Marco A M ; Chen, Liangyi ; Cheng, Heping ; Li, Yulong
Subjects: Acetylcholine ; Acetylcholine - metabolism ; Animals ; Animals, Genetically Modified ; Behavior, Animal - physiology ; Biosensing Techniques - methods ; Biosensors ; Brain ; Brain - metabolism ; Chemical properties ; Cholinergic Agents - pharmacology ; Cholinergic mechanisms ; Cholinergics ; Coupling (molecular) ; Drosophila - genetics ; Drosophila - metabolism ; External stimuli ; G protein-coupled receptors ; Genetic code ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; HEK293 Cells ; Humans ; Mice ; Mushroom Bodies - metabolism ; Neural transmission ; Neuroimaging ; Neurological research ; Neurons - metabolism ; Neurotransmission ; Odor ; Odors ; Olfactory Cortex - metabolism ; Photometry ; Physiological aspects ; Receptor, Muscarinic M3 - genetics ; Receptor, Muscarinic M3 - metabolism ; Sensitivity ; Sensors ; Somatosensory Cortex - metabolism
Is Part Of: Nature methods, 2020-11, Vol.17 (11), p.1139-1146
Description: The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1548-7091
EISSN: 1548-7105
DOI: 10.1038/s41592-020-0953-2
PMID: 32989318
Source: MEDLINE
ProQuest Central

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An optimized acetylcholine sensor for monitoring in vivo cholinergic activity

COPYRIGHT 2020 Nature Publishing Group ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2020. ;ISSN: 1548-7091 ;EISSN: 1548-7105 ;DOI: 10.1038/s41592-020-0953-2 ;PMID: 32989318

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