Evidence map›Paper›PMID 24952910›Full record

ArticleNature methods2014

All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins.

Daniel R Hochbaum, Yongxin Zhao, Samouil L Farhi, Nathan Klapoetke, Christopher A Werley, Vikrant Kapoor, Peng Zou, Joel M Kralj, Dougal Maclaurin, Niklas Smedemark-Margulies and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 461 papers.

0numbers the graph read from it
0cells of the map it votes in
461citing papers in PubMed
30.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

461 citing papers in PubMed, 810 citations in OpenAlex.

  1. Review
  2. Optogenetic tachypacing facilitates burst-induced arrhythmia in stem cell-derived human atrial engineered heart tissue.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
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  6. Article
  7. Review
  8. Article
  9. Excitatory Dysfunction and Phenotypic Rescue in a Human Neuronal Model ofbioRxiv : the preprint server for biology · 2026
    Article
  10. Article
  11. Smart Optogenetics for Real-Time Automated Control of Cardiac Electrical Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  12. Review
  13. Hemodynamic and Electrophysiological Progression of the Rose Bengal Photothrombotic Stroke Model in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  14. Article
  15. Article
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  19. Article
  20. Review

401 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 3 countries.

Daniel R Hochbaum1] Applied Physics Program, School of Engineering and Applied Science, Harvard University, Cambridge, Massachusetts, USA. [2].
Yongxin Zhao1] Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. [2].ORCID 0000000341885725
Samouil L FarhiDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Nathan Klapoetke1] The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. [2] Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts, USA. [4] McGovern Institute for Brain Research, MIT, Cambridge, Massachusetts, USA.
Christopher A WerleyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Vikrant KapoorDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
Peng ZouDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Joel M KraljDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Dougal MaclaurinDepartment of Physics, Harvard University, Cambridge, Massachusetts, USA.
Niklas Smedemark-MarguliesDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Jessica L SaulnierDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Gabriella L BoultingDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Christoph StraubDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Yong Ku Cho1] The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. [2] Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts, USA. [4] McGovern Institute for Brain Research, MIT, Cambridge, Massachusetts, USA.
Michael MelkonianInstitute of Botany, Cologne Biocenter, University of Cologne, Cologne, Germany.
Gane Ka-Shu Wong1] Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada. [2] Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. [3] Beijing Genomics Institute-Shenzhen, Shenzhen, China.
D Jed HarrisonDepartment of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Venkatesh N MurthyDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
Bernardo L Sabatini1] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
Edward S Boyden1] The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. [2] Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts, USA. [4] McGovern Institute for Brain Research, MIT, Cambridge, Massachusetts, USA. [5].
Robert E Campbell1] Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada. [2].ORCID 000000030604092X
Adam E Cohen1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Physics, Harvard University, Cambridge, Massachusetts, USA. [3] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
Harvard University · USUniversity of Alberta · CAMcGovern Institute for Brain Research · USHoward Hughes Medical Institute · USUniversity of Cologne · DE

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
Novel Platforms for Systematic Optical Control of Complex Neural Circuits In VivoR01DA029639 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2010 to 2023
$6.7M
Dendritic Ca signals in striatal medium spiny neuronsR01NS046579 · NINDS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SABATINI, BERNARDO L · 2004 to 2016
$5.0M
SYNAPTIC VESICLE TRAFFICKING IN HIPPOCAMPAL SYNAPSESR01NS039059 · NINDS · HARVARD UNIVERSITY · PI MURTHY, VENKATESH N · 2000 to 2010
$3.3M
Optical sensing of voltage, pH, and small molecules using microbial rhodopsinsDP2OD007428 · OD · HARVARD UNIVERSITY · PI COHEN, ADAM EZRA · 2010 to 2010
$2.5M
Novel Tools and Principles for Precisely Controlling Brain ActivityDP2OD002002 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2007 to 2007
$2.5M
Functional integration of adult-born neurons into the mammalian brainR01DC013329 · NIDCD · HARVARD UNIVERSITY · PI MURTHY, VENKATESH N · 2013 to 2017
$1.8M
Optogenetic studies of mouse olfactionR01DC011291 · NIDCD · HARVARD UNIVERSITY · PI MURTHY, VENKATESH N · 2011 to 2015
$1.7M
CRCNS: Gamma Rhythms and Cell AssembliesR01NS067199 · NINDS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI KOPELL, NANCY · 2009 to 2013
$1.7M
Engineering Microbial Rhodopsins as Optical Voltage SensorsR01EB012498 · NIBIB · HARVARD UNIVERSITY · PI COHEN, ADAM EZRA · 2011 to 2014
$1.5M
Genetically-Encoded Tools for Manipulation of Ion Channel and Receptor FunctionsR01NS075421 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2011 to 2014
$1.3M
CIHRNIBIB NIH HHS 1-R01-EB012498-01NIBIB NIH HHS R01 EB012498NIDA NIH HHS R01 DA029639NIDCD NIH HHS R01 DC011291NIDCD NIH HHS R01 DC013329NIEHS NIH HHS P30 ES002109NIH HHS 1-DP2-OD007428NIH HHS DP2 OD002002NIH HHS DP2 OD007428NINDS NIH HHS R01 NS039059NINDS NIH HHS R01 NS046579NINDS NIH HHS R01 NS067199NINDS NIH HHS R01 NS075421
6 · The paper itself

Abstract

All-optical electrophysiology-spatially resolved simultaneous optical perturbation and measurement of membrane voltage-would open new vistas in neuroscience research. We evolved two archaerhodopsin-based voltage indicators, QuasAr1 and QuasAr2, which show improved brightness and voltage sensitivity, have microsecond response times and produce no photocurrent. We engineered a channelrhodopsin actuator, CheRiff, which shows high light sensitivity and rapid kinetics and is spectrally orthogonal to the QuasArs. A coexpression vector, Optopatch, enabled cross-talk-free genetically targeted all-optical electrophysiology. In cultured rat neurons, we combined Optopatch with patterned optical excitation to probe back-propagating action potentials (APs) in dendritic spines, synaptic transmission, subcellular microsecond-timescale details of AP propagation, and simultaneous firing of many neurons in a network. Optopatch measurements revealed homeostatic tuning of intrinsic excitability in human stem cell-derived neurons. In rat brain slices, Optopatch induced and reported APs and subthreshold events with high signal-to-noise ratios. The Optopatch platform enables high-throughput, spatially resolved electrophysiology without the use of conventional electrodes.

Indexed as

AnimalsDirected Molecular EvolutionMammalsNeuronsRecombinant ProteinsRhodopsinSynaptic TransmissionRecombinant ProteinsRhodopsin

Identifiers

PMID24952910
PMCPMC4117813
OpenAlexW2145909957

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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.