Imaging Voltage in Neurons

In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles, and intrinsic approaches) and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic, or electro-optical phenomena to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods.

[1]  L. Loew,et al.  Absolute spectroscopic determination of cross-membrane potential , 1993, Journal of Fluorescence.

[2]  Walther Akemann,et al.  Engineering of a Genetically Encodable Fluorescent Voltage Sensor Exploiting Fast Ci-VSP Voltage-Sensing Movements , 2008, PloS one.

[3]  Amiram Grinvald,et al.  VSDI: a new era in functional imaging of cortical dynamics , 2004, Nature Reviews Neuroscience.

[4]  F. Bezanilla,et al.  Charge movement of a voltage-sensitive fluorescent protein. , 2009, Biophysical journal.

[5]  J. -. Wu,et al.  Neuronal activity during different behaviors in Aplysia: a distributed organization? , 1994, Science.

[6]  L M Loew,et al.  Second-harmonic imaging microscopy of living cells. , 2001, Journal of biomedical optics.

[7]  T. Sejnowski,et al.  A Compact Multiphoton 3D Imaging System for Recording Fast Neuronal Activity , 2007, PloS one.

[8]  P. Fromherz,et al.  Voltage-sensitive fluorescence of amphiphilic hemicyanine dyes in a black lipid membrane of glycerol monooleate. , 1994, Biochimica et biophysica acta.

[9]  Leonardo Sacconi,et al.  Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy. , 2005, Journal of neurophysiology.

[10]  F. Geiger Second harmonic generation, sum frequency generation, and chi(3): dissecting environmental interfaces with a nonlinear optical Swiss Army knife. , 2009, Annual review of physical chemistry.

[11]  R. Yuste,et al.  Attractor dynamics of network UP states in the neocortex , 2003, Nature.

[12]  S. Antic,et al.  Optical signals from neurons with internally applied voltage-sensitive dyes , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  H. Fuchs,et al.  Chemical Imaging of Interfaces by Sum Frequency Microscopy , 1999 .

[14]  A. Grinvald,et al.  Dynamics of Ongoing Activity: Explanation of the Large Variability in Evoked Cortical Responses , 1996, Science.

[15]  J. Freer,et al.  New Calcium Indicators and Buffers with High Selectivity against Magnesium and Protons : Design , Synthesis , and Properties of Prototype Structures ? , 2001 .

[16]  Jane A Dickerson,et al.  Current Applications of Liquid Chromatography / Mass Spectrometry in Pharmaceutical Discovery After a Decade of Innovation , 2008 .

[17]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[18]  S. Ogawa Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[19]  L M Loew,et al.  Spectra, membrane binding, and potentiometric responses of new charge shift probes. , 1985, Biochemistry.

[20]  Knut Holthoff,et al.  Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons , 2010, The Journal of physiology.

[21]  WG Regehr,et al.  A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  R. Yuste,et al.  Detecting action potentials in neuronal populations with calcium imaging. , 1999, Methods.

[23]  Thomas Knöpfel,et al.  Red-shifted voltage-sensitive fluorescent proteins. , 2009, Chemistry & biology.

[24]  D Yelin,et al.  Laser scanning third-harmonic-generation microscopy in biology. , 1999, Optics express.

[25]  R. Tsien Indicators based on fluorescence resonance energy transfer (FRET). , 2009, Cold Spring Harbor protocols.

[26]  A Grinvald,et al.  Mechanisms of rapid optical changes of potential sensitive dyes. , 1977, Annals of the New York Academy of Sciences.

[27]  N. Shah,et al.  Surface-enhanced Raman spectroscopy. , 2008, Annual review of analytical chemistry.

[28]  L. Brus,et al.  Optical forces between metallic particles. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. Waggoner,et al.  Dye indicators of membrane potential. , 1979, Annual review of biophysics and bioengineering.

[30]  L. Cohen,et al.  Optical monitoring of activity from many areas of the in vitro and in vivo salamander olfactory bulb: a new method for studying functional organization in the vertebrate central nervous system , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  W. N. Ross,et al.  Changes in axon fluorescence during activity: Molecular probes of membrane potential , 1974, The Journal of Membrane Biology.

[32]  M. Chalfie GREEN FLUORESCENT PROTEIN , 1995, Photochemistry and photobiology.

[33]  Rafael Yuste,et al.  Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters , 1991, Neuron.

[34]  L. Cohen,et al.  Optical monitoring of membrane potential: methods of multisite optical measurement. , 1986, Society of General Physiologists series.

[35]  Glenn P. Goodrich,et al.  Plasmonic enhancement of molecular fluorescence. , 2007, Nano letters.

[36]  R. Keynes,et al.  Changes in light scattering associated with the action potential in crab nerves , 1971, The Journal of physiology.

[37]  A. Grinvald,et al.  Neuronal assemblies: Single cortical neurons are obedient members of a huge orchestra , 2003, Biopolymers.

[38]  P. So,et al.  Handbook of Biomedical Nonlinear Optical Microscopy , 2009 .

[39]  E Neher,et al.  Usefulness and limitations of linear approximations to the understanding of Ca++ signals. , 1998, Cell calcium.

[40]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[41]  J. Platt Wavelength Formulas and Configuration Interaction in Brooker Dyes and Chain Molecules , 1956 .

[42]  F Bezanilla,et al.  Charge-shift probes of membrane potential. Characterization of aminostyrylpyridinium dyes on the squid giant axon. , 1985, Biophysical journal.

[43]  W. Denk,et al.  Dendritic spines as basic functional units of neuronal integration , 1995, Nature.

[44]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[45]  W. Denk,et al.  In vivo two-photon voltage-sensitive dye imaging reveals top-down control of cortical layers 1 and 2 during wakefulness , 2008, Proceedings of the National Academy of Sciences.

[46]  A Grinvald,et al.  Visualization of the spread of electrical activity in rat hippocampal slices by voltage‐sensitive optical probes , 1982, The Journal of physiology.

[47]  Rafael Yuste,et al.  Second harmonic imaging of membrane potential of neurons with retinal. , 2004, Journal of biomedical optics.

[48]  Bernd Kuhn,et al.  High sensitivity of Stark-shift voltage-sensing dyes by one- or two-photon excitation near the red spectral edge. , 2004, Biophysical journal.

[49]  W. N. Ross,et al.  Optical recording of neuronal activity in an invertebrate central nervous system: simultaneous monitoring of several neurons. , 1977, Journal of neurophysiology.

[50]  Paul De Weer,et al.  Optical methods in cell physiology , 1986 .

[51]  A. Grinvald,et al.  Linking spontaneous activity of single cortical neurons and the underlying functional architecture. , 1999, Science.

[52]  L M Loew,et al.  Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons. , 1998, Biophysical journal.

[53]  R Y Tsien,et al.  Voltage sensing by fluorescence resonance energy transfer in single cells. , 1995, Biophysical journal.

[54]  David A. DiGregorio,et al.  Submillisecond Optical Reporting of Membrane Potential In Situ Using a Neuronal Tracer Dye , 2009, The Journal of Neuroscience.

[55]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[56]  F. Bezanilla,et al.  Nano to Micro — Fluorescence Measurements of Electric Fields in Molecules and Genetically Specified Neurons , 2005, The Journal of Membrane Biology.

[57]  Daniel A Dombeck,et al.  Optical Recording of Action Potentials with Second-Harmonic Generation Microscopy , 2004, The Journal of Neuroscience.

[58]  Jiang Jiang,et al.  Second-Harmonic Generation Imaging of Membrane Potential with Photon Counting , 2008, Microscopy and Microanalysis.

[59]  L M Loew,et al.  Probing membrane potential with nonlinear optics. , 1993, Biophysical journal.

[60]  M Linial,et al.  Nonlinear optical measurement of membrane potential around single molecules at selected cellular sites. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J Mertz,et al.  Coherent scattering in multi-harmonic light microscopy. , 2001, Biophysical journal.

[62]  W. N. Ross,et al.  Changes in absorption, fluorescence, dichroism, and birefringence in stained giant axons: Optical measurement of membrane potential , 1977, The Journal of Membrane Biology.

[63]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[64]  E. Wanke,et al.  Electric fields at the plasma membrane level: a neglected element in the mechanisms of cell signalling. , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[65]  E. K. Kosmidis,et al.  Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells , 2007, Journal of Neuroscience Methods.

[66]  L. Loew,et al.  Fluorescent indicators of membrane potential: microspectrofluorometry and imaging. , 1989, Methods in cell biology.

[67]  D. Kleinfeld,et al.  Noninvasive detection of changes in membrane potential in cultured neurons by light scattering. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Thomas Knöpfel,et al.  Exploration of Fluorescent Protein Voltage Probes Based on Circularly Permuted Fluorescent Proteins , 2009, Front. Neuroeng..

[69]  R. Tsien,et al.  Fluorescent indicators for Ca2+based on green fluorescent proteins and calmodulin , 1997, Nature.

[70]  Leslie M Loew,et al.  Second harmonic imaging microscopy. , 2003, Methods in enzymology.

[71]  L M Loew,et al.  High-resolution nonlinear optical imaging of live cells by second harmonic generation. , 1999, Biophysical journal.

[72]  Mortazavi,et al.  Supporting Online Material Materials and Methods Figs. S1 to S13 Tables S1 to S3 References Label-free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy , 2022 .

[73]  T. Knöpfel,et al.  Design and characterization of a DNA‐encoded, voltage‐sensitive fluorescent protein , 2001, The European journal of neuroscience.

[74]  Wei Min,et al.  Imaging chromophores with undetectable fluorescence by stimulated emission microscopy , 2009, Nature.

[75]  L M Loew,et al.  Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes. , 1988, Biophysical journal.

[76]  Steven Mennerick,et al.  Diverse Voltage-Sensitive Dyes Modulate GABAAReceptor Function , 2010, The Journal of Neuroscience.

[77]  Rafael Yuste,et al.  Multiphoton stimulation of neurons. , 2002, Journal of neurobiology.

[78]  Vincent A Pieribone,et al.  A genetically targetable fluorescent probe of channel gating with rapid kinetics. , 2002, Biophysical journal.

[79]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[80]  Walther Akemann,et al.  Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins , 2010, Nature Methods.

[81]  Francisco Bezanilla,et al.  A hybrid approach to measuring electrical activity in genetically specified neurons , 2005, Nature Neuroscience.

[82]  A Grinvald,et al.  Improved fluorescent probes for the measurement of rapid changes in membrane potential. , 1982, Biophysical journal.

[83]  A Grinvald,et al.  Optical recording of calcium action potentials from growth cones of cultured neurons with a laser microbeam. , 1981, Science.

[84]  W. N. Ross,et al.  Simultaneous optical measurements of electrical activity from multiple sites on processes of cultured neurons. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[85]  Leslie M. Loew,et al.  Second-harmonic generation of biological interfaces: probing the membrane protein bacteriorhodopsin and imaging membrane potential around GFP molecules at specific sites in neuronal cells of C. elegans , 1999 .

[86]  Ehud Y Isacoff,et al.  A Genetically Encoded Optical Probe of Membrane Voltage , 1997, Neuron.

[87]  Rafael Yuste,et al.  Second harmonic generation in neurons: electro-optic mechanism of membrane potential sensitivity. , 2007, Biophysical journal.

[88]  P. Fromherz,et al.  Spectra of voltage-sensitive fluorescence of styryl-dye in neuron membrane. , 1991, Biochimica et biophysica acta.

[89]  John R. Platt,et al.  Electrochromism, a Possible Change of Color Producible in Dyes by an Electric Field , 1961 .

[90]  R. Tsien A non-disruptive technique for loading calcium buffers and indicators into cells , 1981, Nature.

[91]  D. Kleinfeld,et al.  Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices. , 1997, Cerebral cortex.

[92]  Rafael Yuste,et al.  Imaging membrane potential in dendritic spines. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[93]  L. Stryer,et al.  Retinal has a highly dipolar vertically excited singlet state: implications for vision. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[94]  K. Eisenthal,et al.  Liquid Interfaces Probed by Second-Harmonic and Sum-Frequency Spectroscopy. , 1996, Chemical reviews.