ArticleNature methods2026
Designer indicators for two-photon recording of subthreshold voltage dynamics.
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Article in Nature methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4citing papers in PubMed
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4 citing papers in PubMed.
- A versatile platform for two-photon neuronal population voltage imaging across cortical depths.Nature methods · 2026Article
- A red-emitting, genetically encoded indicator for two-photon voltage recording in vivo.bioRxiv : the preprint server for biology · 2026Article
- Designer indicators for two-photon recording of subthreshold voltage dynamics.Nature methods · 2026Article
- A versatile, positive-going voltage indicator that enables accessible two-photon recordings in vivo.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
- Update of
Authors and funding
34 authors.
Michelle A LandDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5886-9281
Mario Galdamez *Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Vincent Villette *Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.
Jun Zhu *Department of Neuroscience, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7905-7856
Xiaoyu Lu *Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Mate Marosi *Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Shuyuan YangDepartment of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5977-9782
Gregory ForanDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Alex J McDonaldDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1214-3562
Xiaoyu DongDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Elsayed ZaaboutDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5588-3635
Haixin LiuDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Zhuohe LiuSystems, Synthetic and Physical Biology program, Rice University, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1818-646X
Kevin L ColbertDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Shujuan LaiDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Matthew ShoreyDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Anthony S G LourdianeUniversité Paris Cité, Institut Pasteur, AP-HP, INSERM, CNRS, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect, Paris, France.
Annick AyonInstitut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.
Jonathan BradleyInstitut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.ORCID http://orcid.org/0000-0002-6933-1153
Caroline Mailhes-HamonInstitut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.
Ryan G NatanDepartment of Neuroscience, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-3123-4833
Jian ZhongDepartment of Physics, University of California, Berkeley, Berkeley, CA, USA.
Ryan KroegerDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Robert G LawDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Noura HakamDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Cameron L SmithDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2079-4667
Ming HuDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5254-5315
Shanii TabbDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7559-1277
Brice BathellierUniversité Paris Cité, Institut Pasteur, AP-HP, INSERM, CNRS, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect, Paris, France.
Barna DudokDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5078-0090
Na JiDepartment of Neuroscience, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-5527-1663
Laurent BourdieuInstitut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.ORCID http://orcid.org/0000-0003-0195-8758
Jacob ReimerDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4364-8846
François St-PierreDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, USA. stpierre@bcm.edu.ORCID http://orcid.org/0000-0001-8618-4135
Funding
Molecular Engineering of Natural Light-Gated Chloride Channels for Optogenetic InhibitionU01NS118288 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI SPUDICH, JOHN LEE, ST-PIERRE, FRANCOIS · 2020 to 2023
$5.2MENABLING SUBMILLISECOND-TIMESCALE TWO-PHOTON RECORDING OF VOLTAGE DYNAMICS IN THREE DIMENSIONS IN VIVOU01NS133971 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Jacob Reimer, Francois St-Pierre · 2023 to 2026
$4.0MDesigning and deploying an expanded color palette of voltage indicators engineered for multiphoton microscopyU01NS113294 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ST-PIERRE, FRANCOIS, TOLIAS, ANDREAS · 2019 to 2021
$3.7MEngineering photostable fluorescent proteins and biosensors using transcriptomic mining and massive-throughput single-cell screeningR01EB032854 · NIBIB · BAYLOR COLLEGE OF MEDICINE · PI ST-PIERRE, FRANCOIS · 2022 to 2025
$2.4MThe Spatial and Temporal Scale of Neuromodulation in Mouse Sensory CortexRF1NS128901 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI REIMER, JACOB · 2022 to 2022
$2.3MEngineering designer probes for imaging membrane potential: novel parts, architectures, and platformsR01EB027145 · NIBIB · BAYLOR COLLEGE OF MEDICINE · PI ST-PIERRE, FRANCOIS · 2019 to 2022
$2.2MkHz-rate in vivo imaging of neural activity througout the living brainUF1NS107696 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI JI, NA, TSIA, KEVIN KIN MAN · 2018 to 2018
$2.1MOptimizing FACED for robust large-scale activity recordingU01NS137449 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NA Ji · 2024 to 2026
$2.1MAdaptive optical microscopy for high-accuracy recording of neural activity in vivoU01NS118300 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI JI, NA · 2021 to 2023
$1.7MRed-shifted voltage indicators for two-photon all-optical physiology and multi-spectral imagingR01NS136027 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Jacob Reimer, Francois St-Pierre · 2024 to 2026
$1.7MTraining in Neural Control of organ Degeneration and Regeneration (NeuralCODR)T32NS126115 · NINDS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Philip J Horner · 2022 to 2026
$1.4MThe Spatial and Temporal Scale of Neuromodulation in Mouse Sensory CortexR01NS128901 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Jacob Reimer · 2025 to 2026
$1.4MNIBIB NIH HHS R01 EB027145NIBIB NIH HHS R01 EB032854NINDS NIH HHS R00 NS117795NINDS NIH HHS R01 NS128901NINDS NIH HHS R01 NS136027NINDS NIH HHS R34 NS132045NINDS NIH HHS RF1 NS128901NINDS NIH HHS T32 NS126115NINDS NIH HHS U01 NS113294NINDS NIH HHS U01 NS118288NINDS NIH HHS U01 NS118300NINDS NIH HHS U01 NS133971NINDS NIH HHS U01 NS137449NINDS NIH HHS UF1 NS107696NSF | Directorate for Biological Sciences (BIO) 1707359U.S. Department of Health & Human Services | National Institutes of Health (NIH) NS126115U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01EB027145U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01NS113294U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01NS118300Welch Foundation Q-2016-20220331
Abstract
Subthreshold voltage dynamics are essential for neuronal information integration, yet they remain technically challenging to measure in vivo. While genetically encoded voltage indicators are emerging as powerful tools for voltage recording, they lack the sensitivity to detect millivolt-scale subthreshold fluctuations with two-photon microscopy-the method of choice for deep-tissue recording. To overcome this limitation, we engineered two genetically encoded voltage indicators, JEDI3sub and JEDI3hyp, with enhanced subthreshold voltage detection under two-photon excitation. In the mouse brain, JEDI3sub enabled simultaneous tracking of subthreshold optical tuning from over 100 cells simultaneously, while JEDI3hyp captured subthreshold dynamics associated with sharp-wave ripples in hippocampal PV
Indexed as
Microscopy, Fluorescence, MultiphotonNeuronsAnimalsBrainHippocampusInterneuronsMicePhotons
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