Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Liang; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas R.; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen‐Biao; Feng, Guoping

doi:10.1016/j.neuron.2012.07.011

Cited by 199 publications

(184 citation statements)

References 54 publications

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“…18 Six founders were obtained, as verified by PCR genotyping. Consistent with other studies that used the Thy1 promoter to generate transgenic mice, 17,19 (Fig. 1B).…”

Section: Generation and Characterization Of Sumo-kd Micesupporting

confidence: 91%

Neuron-specific Sumo1–3 knockdown in mice impairs episodic and fear memories

Wang

Rodriguiz

Wetsel

et al. 2014

J Psychiatry Neurosci

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“…18 Six founders were obtained, as verified by PCR genotyping. Consistent with other studies that used the Thy1 promoter to generate transgenic mice, 17,19 (Fig. 1B).…”

Section: Generation and Characterization Of Sumo-kd Micesupporting

confidence: 91%

Neuron-specific Sumo1–3 knockdown in mice impairs episodic and fear memories

Wang

Rodriguiz

Wetsel

et al. 2014

J Psychiatry Neurosci

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“…1A (22). Changes in GCaMP fluorescence reflect changes in intracellular calcium, and have been widely shown to correspond to neural spiking activity in studies using two-photon microscopy (22)(23)(24). The kinetics of GCaMP3 and GCaMP6f are similar (25).…”

Section: Resultsmentioning

confidence: 99%

“…Thy1-GCaMP lines were chosen because of their selective expression of calcium-sensitive GCaMP in excitatory pyramidal neurons in cortical layers 2/3 and 5, as shown in Fig. 1A (22). Changes in GCaMP fluorescence reflect changes in intracellular calcium, and have been widely shown to correspond to neural spiking activity in studies using two-photon microscopy (22)(23)(24).…”

Section: Resultsmentioning

confidence: 99%

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Shaik

Kozberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

287

303

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Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by widefield Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI. neurovascular coupling | resting state | GCaMP | optical imaging | neural network activity F unctional magnetic resonance imaging (fMRI) measures local changes in deoxyhemoglobin concentration [HbR] as a surrogate for neural activity. In stimulus-evoked studies, the positive fMRI blood oxygen level-dependent (BOLD) signal corresponds to a decrease in [HbR] caused by a local increase in blood flow leading to over-oxygenation of the region. However, a growing number of studies are now using resting-state functional connectivity fMRI (fc-fMRI) in which spontaneous fluctuations in the BOLD signal are recorded in the absence of a task (1). Spatiotemporal correlations in these hemodynamic signals across the brain have been found to be bilaterally symmetric and synchronized in distant brain regions. This synchrony is interpreted as representing the connectivity of intrinsic neural networks (2-6). Many studies have identified changes in these resting-state networks during brain development (7,8) and in neurological and even psychological disorders (9-11). However, understandin...

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“…Genetically encoded calcium indicators, such as GCaMPs, are a useful tool for measuring intracellular calcium concentration of neurons 58 and have the potential to be used for studying RGC calcium transients after optic nerve transection. Recently, reported work in ex vivo tissue from Thy1-GCaMP3 shows that after optic nerve transection baseline GCaMP3 fluorescence was reduced and the number of GCaMP3-expressing cells decreased.…”

Section: Functional Imaging Of Rgcsmentioning

confidence: 99%

Assessing retinal ganglion cell damage

Smith

Vianna

Chauhan

2017

Eye

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Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.

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Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice

Cited by 199 publications

References 54 publications

Neuron-specific Sumo1–3 knockdown in mice impairs episodic and fear memories

Neuron-specific Sumo1–3 knockdown in mice impairs episodic and fear memories

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Assessing retinal ganglion cell damage

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