On-demand optogenetic activation of human stem-cell-derived neurons

Klapper, Simon D.; Sauter, Evelyn J.; Swiersy, Anka; Hyman, Max A. E.; Bamann, Christian; Bamberg, Ernst; Busskamp, Volker

doi:10.1038/s41598-017-14827-6

Cited by 24 publications

(24 citation statements)

References 39 publications

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“…3a). This wavelength is chosen because it coincides with the action spectrum of the commonly used opsin Channelrhodopsin-2 29,30 . Optical fibres are terminated with a contact site, which serves to couple light into cells cultured directly above.…”

Section: Functional Fibre Developmentmentioning

confidence: 99%

“…We used the fibroblast-derived hiPSC line CRTD5 and modified it to include a Cre-inducible Channelrhodopsin-2-EYFP (enhanced yellow fluorescent protein) expression cassette ( Supplementary Fig. 3a) 29,30 . We generated cardiomyocytes from the modified hiPSC line by modulating the Wnt signalling pathway (Supplementary Fig.…”

Section: Generation Of Optogenetic Hipsc-derived Cardiomyocytesmentioning

confidence: 99%

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Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

et al. 2020

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Bioelectronic interfaces employing arrays of sensors and bioactuators are promising tools for the study, repair and engineering of cardiac tissues. They are typically constructed from rigid and brittle materials processed in a cleanroom environment. An outstanding technological challenge is the integration of soft materials enabling a closer match to the mechanical properties of biological cells and tissues. Here we present an algorithm for direct writing of elastic membranes with embedded electrodes, optical waveguides and microfluidics using a commercial 3D printing system and a palette of silicone elastomers. As proof of principle, we demonstrate interfacing of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs), which are engineered to express Channelrhodopsin-2. We demonstrate electrical recording of cardiomyocyte field potentials and their concomitant modulation by optical and pharmacological stimulation delivered via the membrane. Our work contributes a simple prototyping strategy with potential applications in organ-on-chip or implantable systems that are multi-modal and mechanically soft.

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Section: Functional Fibre Developmentmentioning

confidence: 99%

Section: Generation Of Optogenetic Hipsc-derived Cardiomyocytesmentioning

confidence: 99%

Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

et al. 2020

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“…For example, in 2D, forced expression of neuronal transcription factors, Neu-roD2 or neuroligin-2, can be used to accelerate neuronal maturation, with neural activity occurring after *1 week of neuronal induction. 94,95 Furthermore, optogenetics can be used to increase neural activity and potentially accelerate maturation of hIPSCderived neurons and brain organoids, 96,97 allowing for more rapid assessment of drug-induced changes to neural activity.…”

Section: Drug Screening For Neuroprotective Effects Automated High Comentioning

confidence: 99%

Human-Derived Brain Models: Windows into Neuropsychiatric Disorders and Drug Therapies

Papariello

Litwa

2020

ASSAY and Drug Development Technologies

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Human-derived neurons and brain organoids have revolutionized our ability to model brain development in a dish. In this review, we discuss the potential for human brain models to advance drug discovery for complex neuropsychiatric disorders. First, we address the advantages of human brain models to screen for new drugs capable of altering CNS activity. Next, we propose an experimental pipeline for using human-derived neurons and brain organoids to rapidly assess drug impact on key events in brain development, including neurite extension, synapse formation, and neural activity. The experimental pipeline begins with automated high content imaging for analysis of neurites, synapses, and neuronal viability. Following morphological examination, multi-well microelectrode array technology examines neural activity in response to drug treatment. These techniques can be combined with high throughput sequencing and mass spectrometry to assess associated transcriptional and proteomic changes. These combined technologies provide a foundation for neuropsychiatric drug discovery and future clinical assessment of patient-specific drug responses.

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“…In the case of the experiments that we are presenting, the sample is a two-dimensional random network of human iPSC-derived neurons, which is adherent to a multielectrode array (MEA, 60MEA200/30iR-Ti by Multichannel Systems). The protocol for culturing these neurons, especially the stable expression of ChR2 in stem-cell-derived human neurons, was published recently [33]. In the following, we will focus on different aspects of the setup and the experiments.…”

Section: Holographic Single-cell Illumination Setupmentioning

confidence: 99%

“…The neurons are genetically modified to express wild type ChR2 as well as the coupled fluorescent dye Enhanced Yellow Fluorescent Protein (EYFP) and form a two-dimensional (2D) layer which is adherent to a multielectrode array (MEA) [33]. These devices are used to noninvasively record the extracellular electrical signals of neurons.…”

Section: Samplementioning

confidence: 99%

Optogenetic Stimulation of Human Neural Networks Using Fast Ferroelectric Spatial Light Modulator—Based Holographic Illumination

et al. 2018

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Abstract:The generation and application of human stem-cell-derived functional neural circuits promises novel insights into neurodegenerative diseases. These networks are often studied using stem-cell derived random neural networks in vitro, with electrical stimulation and recording using multielectrode arrays. However, the impulse response function of networks is best obtained with spatiotemporally well-defined stimuli, which electrical stimulation does not provide. Optogenetics allows for the functional control of genetically altered cells with light stimuli at high spatiotemporal resolution. Current optogenetic investigations of neural networks are often conducted using full field illumination, potentially masking important functional information. This can be avoided using holographically shaped illumination. In this article, we present a digital holographic illumination setup with a spatial resolution of about 8 µm, which suffices for the stimulation of single neurons, and offers a temporal resolution of less than 0.6 ms. With this setup, we present preliminary single-cell stimulation recording of stem-cell derived induced human neurons in a random neural network. This will offer the opportunity for further studies on connectivity in such networks.

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On-demand optogenetic activation of human stem-cell-derived neurons

Cited by 24 publications

References 39 publications

Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

Human-Derived Brain Models: Windows into Neuropsychiatric Disorders and Drug Therapies

Optogenetic Stimulation of Human Neural Networks Using Fast Ferroelectric Spatial Light Modulator—Based Holographic Illumination

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