An optimized acetylcholine sensor for monitoring in vivo cholinergic activity
Document Type
Article
Publication Date
11-1-2020
Journal
Nature Methods
Volume
17
Issue
11
First Page
1139
Last Page
1146
URL with Digital Object Identifier
10.1038/s41592-020-0953-2
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRABACh (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.
Notes
An author-accepted manuscript is available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606762/