Genetically Encoded Voltage Indicators: Opportunities and Challenges.
A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution.



Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions.
Department of Neurobiology, Stanford University, Stanford, California 94305.
Helen H
0000-0001-5140-9664
HH
Yang
Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, and Department of Electrical and Computer Engineering, Rice University, Houston, Texas 77005 stpierre@bcm.edu.
François
0000-0001-8618-4135
F
St-Pierre
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001931:Brain Mapping / Q000379:methods; D031541:Fluorescence Resonance Energy Transfer / Q000639:trends*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics*; D008564:Membrane Potentials / Q000502:physiology*; D062308:Optogenetics / Q000639:trends*; D013673:Technology Assessment, Biomedical; D056969:Voltage-Sensitive Dye Imaging / Q000639:trends*
D008164:Luminescent Proteins
biosensors; fluorescence imaging; genetically encoded voltage indicators (GEVI); voltage imaging
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