Title

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.

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