ArticleNeuron2023
Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator.
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Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82citing papers in PubMed
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82 citing papers in PubMed, 122 citations in OpenAlex.
- CLOK: a chemigenetic multicolor labeling system to visualize neuronal birthdate and circuit integration.Nature neuroscience · 2026Article
- Methods, Trade-offs, and Opportunities in High-speed Optical Microscopy for Neural Voltage imaging.Nature photonics · 2026Article
- Crosstalk-free optical indicator-actuator combinations for bidirectional optogenetics.npj biomedical innovations · 2026Review
- Voltage dynamics of cortical dendrites in vivo.Nature neuroscience · 2026Article
- Connectomic evidence that ordered activity drives neuromuscular network formation.Nature neuroscience · 2026Article
- Absolute voltage mapping using dynamic photocycle control.bioRxiv : the preprint server for biology · 2026Article
- Article
- Combining sampling and attractor dynamics in spiking models of head direction systems.PLoS computational biology · 2026Article
- Three-dimensional voltage imaging in live larval zebrafish brains using fully genetically encoded voltage indicator.Scientific reports · 2026Article
- A multimodal adaptive optical microscope for in vivo imaging from molecules to organisms.Nature methods · 2026Article
- Intrinsic space-time couplings governing multi-scale cortical dynamics.bioRxiv : the preprint server for biology · 2026Article
- Causal and directional elements of global brain dynamics.bioRxiv : the preprint server for biology · 2026Article
- Adapting a Two-Photon Scanning Microscope for Simultaneous Single-Photon Imaging of an Infrared Dopamine Sensor.eNeuro · 2026Article
- Cerebral capillary computation.American journal of physiology. Cell physiology · 2026Review
- Distinct cell-type contributions and network topography of theta-nested gamma oscillations in the medial entorhinal cortex.bioRxiv : the preprint server for biology · 2026Article
- Isotonic and minimally invasive optical clearing media for live cell imaging ex vivo and in vivo.Nature methods · 2026Article
- Injury-induced electrochemical coupling triggers organ growth.Science advances · 2026Article
- Voltage imaging in zebrafish using high-speed light-sheet microscopy.Neurophotonics · 2026Review
- Voltage imaging as a window into neural computation.Neurophotonics · 2026Article
- Glutamate indicators with increased sensitivity and tailored deactivation rates.Nature methods · 2026Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 7 institutions in 3 countries.
Ahmed S AbdelfattahJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: ahmed_abdelfattah@brown.edu.
Jihong ZhengJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Amrita SinghJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Yi-Chieh HuangInstitute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Daniel ReepJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Getahun TsegayeJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Arthur TsangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Benjamin J ArthurJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Monika RehorovaDepartment of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Carl V L OlsonDepartment of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Yichun ShuaiJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Lixia ZhangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Tian-Ming FuJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Daniel E MilkieJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Maria V MoyaDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.
Timothy D WeberDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.
Andrew L LemireJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Christopher A BakerAllen Institute for Brain Science, Seattle, WA, USA.
Natalie FalcoJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Qinsi ZhengJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Jonathan B GrimmJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Mighten C YipGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Deepika WalpitaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Martin ChasePortland, OR, USA.
Luke CampagnolaAllen Institute for Brain Science, Seattle, WA, USA.
Gabe J MurphyAllen Institute for Brain Science, Seattle, WA, USA.
Allan M WongJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Craig R ForestGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Jerome MertzDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.
Michael N EconomoDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.
Glenn C TurnerJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Minoru KoyamaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Bei-Jung LinInstitute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Eric BetzigJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; Departments of Molecular and Cell Biology and Physics, Howard Hughes Medical Institute, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Ondrej NovakDepartment of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Luke D LavisJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Karel SvobodaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Wyatt KorffJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Tsai-Wen ChenInstitute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: chentw@nycu.edu.tw.
Eric R SchreiterJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: schreitere@janelia.hhmi.org.
Jeremy P HassemanJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: hassemanj@janelia.hhmi.org.
Ilya KolbJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: kolbi@janelia.hhmi.org.
Howard Hughes Medical Institute · USBoston University · USAllen Institute for Brain Science · USCharles University · CZNational Yang Ming Chiao Tung University · TWGeorgia Institute of Technology · USOregon Medical Research Center · US
Funding
Lighting up the brain: Optogenetic tools to record, trace, and manipulate brain circuits at cellular resolutionDP2MH129956 · NIMH · BROWN UNIVERSITY · PI ABDELFATTAH, AHMED · 2021 to 2024
$2.4MAutomated cell-type-specific electrophysiology for understanding circuit dysregulation in Alzheimer's DiseaseRF1AG079269 · NIA · EMORY UNIVERSITY · PI FOREST, CRAIG, ROWAN, MATTHEW J.M. · 2022 to 2024
$2.4MScalable Cell- and Circuit-Targeted ElectrophysiologyR01NS102727 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., FOREST, CRAIG · 2017 to 2020
$2.2MChemigenetic voltage indicators for far-red and two-photon imaging in vivoRF1NS133755 · NINDS · BROWN UNIVERSITY · PI ABDELFATTAH, AHMED · 2023 to 2023
$2.2MFast, large-scale neuronal imaging with multi-z confocal microscopyR01EB029171 · NIBIB · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MERTZ, JEROME · 2020 to 2023
$1.8MHigh-throughput mapping of synaptic connectivity between transcriptomically defined cell typesRF1MH126882 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI ECONOMO, MICHAEL NICHOLAS · 2022 to 2022
$1.4MA Scalable Method for Mapping Microconnectivity in Transcriptomically Distinct Neuron TypesF32MH129149 · NIMH · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MOYA, MARIA VICTORIA · 2022 to 2024
$150kHoward Hughes Medical InstituteNIA NIH HHS RF1 AG079269NIBIB NIH HHS R01 EB029171NIMH NIH HHS DP2 MH129956NIMH NIH HHS F32 MH129149NIMH NIH HHS RF1 MH126882NINDS NIH HHS R01 NS102727NINDS NIH HHS RF1 NS133755
Abstract
The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, although with lower baseline fluorescence. In multiple in vitro and in vivo comparisons with its predecessor across multiple species, we found Voltron2 to be more sensitive to APs and subthreshold fluctuations. Finally, we used Voltron2 to study and evaluate the possible mechanisms of interneuron synchronization in the mouse hippocampus. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability.
Indexed as
Angiotensin-Converting Enzyme 2RhodopsinAction PotentialsAnimalsMiceMutationNeuronsAngiotensin-Converting Enzyme 2Rhodopsinbiosensorsfluorescence imagingfluorescent proteinsgenetically encoded indicatorsvoltage imaging
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.