title: High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor.
abstract: Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Previous GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores through resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than previous GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy.
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. yiyang.gong@duke.edu mschnitz@stanford.edu.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Gong
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jin Zhong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Grewe
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eismann
authors.affiliation: James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. yiyang.gong@duke.edu mschnitz@stanford.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schnitzer
mesh_terms: D000200:Action Potentials; D000818:Animals; D060807:Bioluminescence Resonance Energy Transfer Techniques; D015374:Biosensing Techniques; D003712:Dendrites / Q000502:physiology; D004331:Drosophila melanogaster / Q000502:physiology; D005073:Evoked Potentials, Somatosensory; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics; D012903:Smell
chemical_list: D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012243:Rhodopsin