An R-CaMP1.07 reporter mouse for cell-type-specific expression of a sensitive red fluorescent calcium indicator

Bethge, Philipp; Carta, Stefano; Lorenzo, Dayra A.; Egolf, Ladan; Goniotaki, Despoina; Madisen, Linda; Voigt, Fabian F.; Chen, Jerry L.; Schneider, Bernard L.; Ohkura, Masamichi; Nakai, Junichi; Zeng, Hongkui; Aguzzi, Adriano; Helmchen, Fritjof

doi:10.1371/journal.pone.0179460

Cited by 50 publications

(57 citation statements)

References 70 publications

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“…Such laminar-specific connectivity suggests different functional roles of superficial and deep-layer neurons in S1. In line with this notion, recent studies that directly compared sensory processing across layers have started to uncover functional distinctions within the laminar organization (van der Bourg et al, 2016;de Kock and Sakmann, 2009;O'Connor et al, 2010;Pluta et al, 2015;.…”

Section: Introductionmentioning

confidence: 91%

“…To measure neuronal activity across cortical layers we injected AAV2.1-EFα1-R-CaMP1.07 into barrel cortex of adult mice, causing expression of the genetically encoded calcium indicator R-CaMP1.07 (Bethge et al, 2017;Ohkura et al, 2012) in L2/3 and L5 neurons ( Figure 1C; Experimental Procedures). R-CaMP1.07-expressing cells presumably mainly represent pyramidal neurons as similar viral vectors previously barely drove expression in GABAergic interneurons (Chen et al, 2013).…”

Section: Calcium Imaging Across Barrel Cortex Layers In a Tactile Virmentioning

confidence: 99%

“…Figure 1D and E show example calcium transients measured in neuronal subpopulations in L2/3 and L5 in freely running mice. Assuming single action potential-evoked R-CaMP1.07 ΔF/F changes of ~7% amplitude with ~0.3 s decay time constant (Bethge et al, 2017) and linear summation, a 50% steady-state ΔF/F change reflects a firing rate change of about 24 Hz (Helmchen et al, 1996) whereas sharp large calcium transients indicate the occurrence of bursts with variable numbers of action potentials.…”

Section: Calcium Imaging Across Barrel Cortex Layers In a Tactile Virmentioning

confidence: 99%

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Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex

Ayaz

Stäuble

Saleem

et al. 2018

Preprint

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During navigation rodents continually sample the environment with their whiskers. How locomotion modulates neuronal activity in somatosensory cortex and how self-motion is integrated with whisker touch remains unclear. Here, we used calcium imaging in mice running in a tactile virtual reality to investigate modulation of neurons in layer 2/3 (L2/3) and L5 of barrel cortex. About a third of neurons in both layers increased activity during running and concomitant whisking, in the absence of touch. Fewer neurons were modulated by whisking alone (<10%). Whereas L5 neurons responded transiently to wall-touching during running, L2/3 neurons showed sustained activity after touch onset. Consistently, neurons encoding running-with-touch were more abundant in L2/3 compared to L5. Few neurons across layers were also sensitive to abrupt perturbations of tactile flow. We propose that L5 neurons mainly report changes in touch conditions whereas L2/3 neurons continually monitor ongoing tactile stimuli during running.

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Section: Introductionmentioning

confidence: 91%

Section: Calcium Imaging Across Barrel Cortex Layers In a Tactile Virmentioning

confidence: 99%

Section: Calcium Imaging Across Barrel Cortex Layers In a Tactile Virmentioning

confidence: 99%

See 1 more Smart Citation

Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex

Ayaz

Stäuble

Saleem

et al. 2018

Preprint

Self Cite

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“…Over the last few years there has been a sharp increase in the number of mouse lines with GCaMP expression throughout much of neocortex (Hasan et al , 2004; Chen et al , 2012; Zariwala et al , 2012; Madisen et al 2015; Wekselblatt et al , 2016; Bethge et al , 2017; Daigle et al , 2018), offering the opportunity to image cortical activity with high signal-to-noise and genetically-targeted expression. As a result, there has been a resurgence in the use of widefield fluorescence calcium imaging to monitor brain dynamics in vivo , especially in the context of mouse behavior (Wekselblatt et al , 2016; Makino et al , 2017; Allen et al, 2017, Mitra et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Separation of hemodynamic signals from GCaMP fluorescence measured with widefield imaging

Valley

Moore

Zhuang

et al. 2019

Preprint

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23Widefield calcium imaging is often used to measure brain dynamics in behaving mice. With a large 24 field of view and a high sampling rate, widefield imaging can monitor activity from several distant 25 cortical areas simultaneously, revealing cortical interactions. Interpretation of widefield images is 26 complicated, however, by the absorption of light by hemoglobin, which can substantially affect the 27 measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multi-28 wavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, 29 we develop a spatially-detailed regression-based method to estimate hemodynamics. The spatially-30 detailed model is based on a linear form of the Beer-Lambert relationship, but is fit at every pixel in the 31 image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, 32 the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence.33 The improvement is pronounced near blood vessels and, in contrast with other models based on 34 regression or the Beer-Lambert law, can remove vascular artifacts along the sagittal midline. Compared to 35 other separation approaches, the spatially-detailed model permits more accurate fluorescence-based 36 determination of neuronal activity across the cortex.37

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“…Expression patterns and levels are reproducible across different individual animals (Zariwala, Borghuis et al 2012, Dana, Chen et al 2014. Multiple transgenic GECI lines have been developed using different transgene insertion techniques (Hasan, Friedrich et al 2004, Díez-García, Matsushita et al 2005, Tallini, Ohkura et al 2006, Heim, Garaschuk et al 2007, Tallini, Brekke et al 2007, Atkin, Patel et al 2009, Chen, Cichon et al 2012, Direnberger, Mues et al 2012, Zariwala, Borghuis et al 2012, Dana, Chen et al 2014, Madisen, Garner et al 2015, Wekselblatt, Flister et al 2016, Bethge, Carta et al 2017, Daigle, Madisen et al 2017. Cre recombinase-responsive reporter lines can be used in combination with Cre-expressing driver lines to flexibly express GECIs in specific cell types.…”

Section: Introductionmentioning

confidence: 99%

Thy1transgenic mice expressing the red fluorescent calcium indicator jRGECO1a for neuronal population imagingin vivo

Dana

Novák

Guardado-Montesino

et al. 2018

Preprint

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Calcium imaging is commonly used to measure the neural activity of large groups of neurons in mice. Genetically encoded calcium indicators (GECIs) can be delivered for this purpose using non-invasive genetic methods. Compared to viral gene transfer, transgenic targeting of GECIs provides stable long-term expression and obviates the need for invasive viral injections. Transgenic mice expressing the green GECI GCaMP6 are already widely used. Here we present the generation and characterizarion of transgenic mice expressing the sensitive red GECI jRGECO1a, driven by the Thy1 promoter. Four transgenic lines with different expression patterns showed sufficiently high expression for cellular in vivo imaging. We used two-photon microscopy to characterize visual responses of individual neurons in the visual cortex in vivo. The signal-to-noise ratio in transgenic mice was comparable to, or better than, for mice transduced with adeno-associated virus.We also show that Thy1-jRGECO1a transgenic . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/284497 doi: bioRxiv preprint first posted online Mar. 18, 2018; mice are useful for transcranial population imaging and functional mapping using widefield fluorescecnce microscopy. We also demonstrate imaging of visual responses in retinal ganglion cells. Thy1-jRGECO1a transgenic mice are therefore a useful addition to the toolbox for imaging activity in intact neural networks.

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An R-CaMP1.07 reporter mouse for cell-type-specific expression of a sensitive red fluorescent calcium indicator

Cited by 50 publications

References 70 publications

Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex

Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex

Separation of hemodynamic signals from GCaMP fluorescence measured with widefield imaging

Thy1transgenic mice expressing the red fluorescent calcium indicator jRGECO1a for neuronal population imagingin vivo

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