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. 2019 Sep 12;17:71. doi: 10.1186/s12915-019-0682-0

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© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 4 — Chemogenetic voltage indicators. a Schematic representation of hVOS, consisting of a fluorescent protein anchored to the plasma membrane, combined with a non-fluorescent synthetic compound dipicrylamine (DPA), which serves as a voltage-sensitive FRET acceptor. b Cellular resolution voltage imaging with hVOS. Hippocampal slices from hVOS::Fos mouse expressing hVOS probe in granule cells in a Cre-Fos-dependent manner. Left: Fluorescence in brain sections after crossing Ai35-hVOS with Cre-Fos mice showing hVOS-expressing neurons in the granule cell layer of the hippocampus. Right: Response in four neurons in a hippocampal slice from an hVOS::Fos mouse to electrical stimulation. c Schematic representation of VoltageSpy, consisting of the expression of SpyCatcher on the cellular surface and the subsequent extracellular interaction with the VF dye. d Subcellular voltage imaging with VoltageSpy. Cultured hippocampal neurons co-expressing SpyCatcher and nuclear mCherry and labeled with VoltageSpy were captured at 500 Hz under widefield fluorescence microscopy. Left: VoltageSpy is shown in green and nuclear staining in red. Middle: Higher magnifications of selected dendritic regions. Scale bar 20 μm. Right: Voltage imaging in dendrites showing evoked action potentials in selected ROIs, coded by colors indicated in the panel. Images and traces modified with permission from [69] (b) and [82] (d)