Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

Borden, Peter Y.; Ortiz, Alex D.; Waiblinger, Christian; Sederberg, Audrey; Morrissette, Arthur E.; Forest, Craig R.; Jaeger, Dieter; Stanley, Garrett B.

doi:10.1117/1.nph.4.3.031212

Cited by 30 publications

(31 citation statements)

References 70 publications

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“…S1B ). Monochromatic GEVI or GECI optical signals obtained with mesoscopic widefield imaging are known to be contaminated by intrinsic activity-dependent optical signals, and a variety of approaches have been used to account for this confound 12 , 20 , 22 – 25 . Here we used a differential dual emission indicator that reports membrane voltage by the anticorrelated changes in fluorescence intensity of FRET donor (mCitrine) and acceptor (mKate2) fluorescent proteins (FPs) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Cortical signatures of wakeful somatosensory processing

Song

Piscopo

Niell

et al. 2018

Sci Rep

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Sensory inputs carry critical information for the survival of an organism. In mice, tactile information conveyed by the whiskers is of high behavioural relevance, and is broadcasted across cortical areas beyond the primary somatosensory cortex. Mesoscopic voltage sensitive dye imaging (VSDI) of cortical population response to whisker stimulations has shown that seemingly ‘simple’ sensory stimuli can have extended impact on cortical circuit dynamics. Here we took advantage of genetically encoded voltage indicators (GEVIs) that allow for cell type-specific monitoring of population voltage dynamics in a chronic dual-hemisphere transcranial windowed mouse preparation to directly compare the cortex-wide broadcasting of sensory information in wakening (lightly anesthetized to sedated) and awake mice. Somatosensory-evoked cortex-wide dynamics is altered across brain states, with anatomically sequential hyperpolarising activity observed in the awake cortex. GEVI imaging revealed cortical activity maps with increased specificity, high spatial coverage, and at the timescale of cortical information processing.

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Section: Resultsmentioning

confidence: 99%

“…Optical monitoring using differential dual emission GEVIs (Fig. 1E ) offers the advantage of improved separation of haemodynamic and voltage signals, which can be problematic for monochromatic in vivo widefield optical imaging experiments in the mammalian brain 12 , 20 , 22 – 25 .…”

Section: Discussionmentioning

confidence: 99%

Cortical signatures of wakeful somatosensory processing

Song

Piscopo

Niell

et al. 2018

Sci Rep

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“…While ArcLight has relatively slow kinetics (~10ms fast time constant), which limits its ability to detect high-frequency spiking activity, it is extremely bright, sensitive, and has been shown to respond to neuronal activity in vivo. This includes in vivo application in Drosophila, worm, mouse, and even plants [10,11,17,18,[37][38][39]. Previous imaging studies using ArcLight in mice used either in utero electroporation or AAV viral vectors under the control of different promoters (hSyn and CAG).…”

Section: Discussionmentioning

confidence: 99%

Voltage imaging using transgenic mouse lines expressing the GEVI ArcLight in two olfactory cell types

Platisa

Zeng

Madisen

et al. 2020

Preprint

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Genetically encoded voltage indicators (GEVIs) allow for cell-specific optical recordings of membrane potential changes in defined cell populations. One tool that would further their use in the in vivo mammalian brain is transgenic reporter animals that facilitate precise and repeatable targeting with high expression levels. The present literature on the development and use of transgenic mouse lines as vehicles for GEVI expression is limited. Here we report the first in vivo experiments using a transgenic reporter mouse for the GEVI ArcLight (Ai86(TITL-ArcLight)), which utilizes a Cre/tTA dependent expression system (TIGRE 1.0). Following pairing to appropriate Cre- and tTA transgenic mice, we report two mouse lines with ArcLight expression restricted to olfactory sensory neurons (OMP-ArcLight), and a subpopulation of interneurons that include periglomerular and granule cells (Emx1-ArcLight) in the olfactory bulb (OB). The ArcLight expression in these lines was sufficient for in vivo imaging of odorant responses in single trials. Odor responses were measured in the OB using epifluorescence and 2-photon imaging. The voltage responses were odor-specific and concentration-dependent, and confirmed earlier conclusions from calcium measurements. This study shows that the ArcLight Ai86(TITL-ArcLight) transgenic line is a flexible genetic tool that can be used to record neuronal electrical activity of a variety of cell types with a signal-to-noise ratio that is comparable to previous reports using viral transduction.

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“…Over the last several decades, neuroscientists have made significant strides to understand how neuronal computations occurring in isolated circuits in the brain mediate behavior. More recently, the advent of genetically encoded calcium 1 and voltage indicators 2,3 , along with transgenic approaches for broadly expressing these indicators in the brain in a cell-type specific fashion 4,5 has enabled mesoscale imaging of multiple cortical regions simultaneously [6][7][8] . These studies have revealed how neural activity across multiple regions of the cortex are coordinated in a variety of brain states and behaviors [9][10][11][12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

Rynes

Surinach

Linn

et al. 2020

Preprint

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The advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.

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Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

Cited by 30 publications

References 70 publications

Cortical signatures of wakeful somatosensory processing

Cortical signatures of wakeful somatosensory processing

Voltage imaging using transgenic mouse lines expressing the GEVI ArcLight in two olfactory cell types

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

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