Comparative Evaluation of Genetically Encoded Voltage Indicators

Bandô, Yoshio; Sakamoto, Masayuki; Kim, Samuel; Ayzenshtat, Inbal; Yuste, Rafael

doi:10.1016/j.celrep.2018.12.088

Cited by 150 publications

(145 citation statements)

References 63 publications

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“…Importantly, it is not clear whether the increased fluorescence intensity is a result of greater 1:1 entrainment, or due to other activation properties such as bursting. Newer developments in genetically encoded voltage (GEVI) and calcium indicators (GECI) with faster kinetics may be able to more comprehensively address these questions [93][94][95]. However, it should be noted that current GEVIs do not provide comparable spatial resolution and suffer from lower signal to noise ratio [96].…”

Section: Limitationsmentioning

confidence: 99%

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Steiger

Eles

Ludwig

et al. 2019

Preprint

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250 word maximum Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e. increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10 Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.Significance Statement: Electrical stimulation has promise to restore sensation and motor function, as well as treat the symptoms of several neurological disorders. However, the mechanisms responsible for the beneficial effects of stimulation are not fully understood. This work supports modeling predictions by demonstrating that modulation of the stimulation waveform dramatically affects the spatial recruitment and activity level of neurons in vivo. These findings suggest that stimulation waveform symmetry represents a parameter that may be able to increase the dynamic range of stimulation ap-plications. Further characterization of these parameters with frequency, and amplitude could provide further insight into the mechanisms of electrical stimulation.

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Section: Limitationsmentioning

confidence: 99%

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Steiger

Eles

Ludwig

et al. 2019

Preprint

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“…For example, recent studies have demonstrated that opsin-based GEVIs (i.e. Ace2N-2AA-mNeon, MacQ-mCitrine) do not work under multiphoton illumination, the technique of choice for deep tissue imaging necessary in highly scattering media such as the mammalian brain 8,14,15 .…”

Section: Introductionmentioning

confidence: 99%

Different categories of fluorescent proteins result in GEVIs with similar characteristics

Platisa

Zhou

Pieribone

2020

Preprint

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The latest generation of genetically encoded voltage indicators (GEVIs) is significantly advancing our ability to study electrical activity from large numbers of identified neurons. The further refinement of the technology will contribute to our understanding of behavior-evoked information perception, transfer and processing on a cellular level across brain regions. The development of GEVIs relies on synthetic biology which includes rational and random modifications of indicator sequence. One strategy in GEVI design is based on creating chimeras between voltage sensitive protein domains (VSDs) and fluorescent proteins (FPs). However, in this design scenario, the mechanistic details of voltage-induced fluorescence change that would inform rational design and improvements of GEVIs are still largely missing. Here we preformed a systematic study of how nature of the FP and altering the insertion site affects the characteristics of Ciona intestinalis voltage-sensitive phosphatase-based GEVIs. Surprisingly, we found that regardless of vast difference in phylogenesis, biochemical properties, fluorophore structure, sequence and excitation/emission spectra between FPs, the resulting GEVIs exhibit virtually identical decrease in fluorescence intensity in response to depolarization. These results stand in strong contrast to studies demonstrating that small numbers of targeted mutations in the FP sequence cause dramatic changes in both signal size and polarity.

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“…1(b)], leading to a halving of the maximum frame rate. This limitation becomes important when investigating fast events such as calcium transients 12,13 or very large volumes, 4,9,[14][15][16] but can be overcome by generating two independent parallel light-sheets within the field of view (FOV) and by synchronizing them with the two rolling shutters, at the cost of increased complexity. A first such system has been realized using a DLSM 17 where two focused illuminating beams, coming from two identical but facing each other objectives, scan half the FOV each in opposite directions.…”

Section: Introductionmentioning

confidence: 99%

Dual-beam confocal light-sheet microscopy via flexible acousto-optic deflector

Gavryusev¹,

Sancataldo²,

Ricci³

et al. 2019

J. Biomed. Opt.

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Confocal detection in digital scanned laser light-sheet fluorescence microscopy (DSLM) has been established as a gold standard method to improve image quality. The selective line detection of a complementary metal-oxide-semiconductor camera (CMOS) working in rolling shutter mode allows the rejection of out-of-focus and scattered light, thus reducing background signal during image formation. Most modern CMOS have two rolling shutters, but usually only a single illuminating beam is used, halving the maximum obtainable frame rate. We report on the capability to recover the full image acquisition rate via dual confocal DSLM by using an acoustooptic deflector. Such a simple solution enables us to independently generate, control and synchronize two beams with the two rolling slits on the camera. We show that the doubling of the imaging speed does not affect the confocal detection high contrast.

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Comparative Evaluation of Genetically Encoded Voltage Indicators

Cited by 150 publications

References 63 publications

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Different categories of fluorescent proteins result in GEVIs with similar characteristics

Dual-beam confocal light-sheet microscopy via flexible acousto-optic deflector

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