Open-cell recording of action potentials using active electrode arrays

AbstractMulti-electrode arrays (MEAs) have been used for many years to measure electrical activity in ensembles of many hundreds of neurons, and are used in research areas as diverse as neuronal connectivity and drug discovery. A high sampling frequency is required to adequately capture action potentials, also known as spikes, the primary electrical event associated with neuronal activity, and the resulting raw data files are large and difficult to visualize with traditional plotting tools. Many common approaches to deal with this issue, such as extracting spikes times and solely performing spike train analysis, significantly reduce data dimensionality. Unbiased data exploration benefits from the use of tools that minimize data transforms and such tools enable the development of heuristic perspective from data prior to any subsequent processing. Here we introduce MEA Viewer, a high-performance interactive application for the direct visualization of multi-channel electrophysiological data. MEA Viewer provides many high-performance visualizations of electrophysiological data, including an easily navigable overview of all recorded extracellular signals overlaid with spike timestamp data and an interactive raster plot. Beyond the fundamental data displays, MEA Viewer can signal average and spatially overlay the extent of action potential propagation within single neurons. This view extracts information below the spike detection threshold to directly visualize the propagation of action potentials across the plane of the MEA. This entirely new method of using MEAs opens up new and novel research applications for medium density arrays. MEA Viewer is licensed under the General Public License version 3, GPLv3, and is available at http://github.com/dbridges/mea-tools.

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Mechanism of Irregular Firing of Suprachiasmatic Nucleus Neurons in Rat Hypothalamic Slices

Journal of Neurophysiology ◽

10.1152/jn.00314.2003 ◽

2004 ◽

Vol 91 (1) ◽

pp. 267-273 ◽

Cited By ~ 41

Author(s):

Nikolai I. Kononenko ◽

F. Edward Dudek

Keyword(s):

Suprachiasmatic Nucleus ◽

Action Potentials ◽

Interspike Interval ◽

Inhibitory Postsynaptic Potentials ◽

Irregular Pattern ◽

Cell Recording ◽

Spontaneous Action ◽

Spontaneous Action Potentials ◽

Hypothalamic Slices ◽

Irregular Firing

The mechanisms of irregular firing of spontaneous action potentials in neurons from the rat suprachiasmatic nucleus (SCN) were studied in hypothalamic slices using cell-attached and whole cell recording. The firing pattern of spontaneous action potentials could be divided into regular and irregular, based on the interspike interval (ISI) histogram and the membrane potential trajectory between action potentials. Similar to previous studies, regular neurons had a firing rate about >3.5 Hz and irregular neurons typically fired about <3.5 Hz. The ISI of irregular-firing neurons was a linear function of the sum of inhibitory postsynaptic potentials (IPSPs) between action potentials. Bicuculline (10–30 μM) suppressed IPSPs and converted an irregular pattern to a more regular firing. Bicuculline also depolarized SCN neurons and induced bursting-like activity in some SCN neurons. Gabazine (20 μM), however, suppressed IPSPs without depolarization, and also converted irregular activity to regular firing. Thus GABAA receptor–mediated IPSPs appear responsible for irregular firing of SCN neurons in hypothalamic slices.

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Two-Photon Excitation of Potentiometric Probes Enables Optical Recording of Action Potentials From Mammalian Nerve Terminals In Situ

Journal of Neurophysiology ◽

10.1152/jn.00929.2007 ◽

2008 ◽

Vol 99 (3) ◽

pp. 1545-1553 ◽

Cited By ~ 49

Author(s):

Jonathan A. N. Fisher ◽

Jonathan R. Barchi ◽

Cristin G. Welle ◽

Gi-Ho Kim ◽

Paul Kosterin ◽

...

Keyword(s):

Action Potentials ◽

Optical Recording ◽

Photon Absorption ◽

Nerve Terminals ◽

Electrode Arrays ◽

Two Photon ◽

Photon Excitation ◽

Mammalian Nerve ◽

Two Photon Excitation

We report the first optical recordings of action potentials, in single trials, from one or a few (∼1–2 μm) mammalian nerve terminals in an intact in vitro preparation, the mouse neurohypophysis. The measurements used two-photon excitation along the “blue” edge of the two-photon absorption spectrum of di-3-ANEPPDHQ (a fluorescent voltage-sensitive naphthyl styryl-pyridinium dye), and epifluorescence detection, a configuration that is critical for noninvasive recording of electrical activity from intact brains. Single-trial recordings of action potentials exhibited signal-to-noise ratios of ∼5:1 and fractional fluorescence changes of up to ∼10%. This method, by virtue of its optical sectioning capability, deep tissue penetration, and efficient epifluorescence detection, offers clear advantages over linear, as well as other nonlinear optical techniques used to monitor voltage changes in localized neuronal regions, and provides an alternative to invasive electrode arrays for studying neuronal systems in vivo.

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Flexible active electrode arrays with ASICs that fit inside the rat’s spinal canal

Biomedical Microdevices ◽

10.1007/s10544-015-0011-5 ◽

2015 ◽

Vol 17 (6) ◽

Cited By ~ 10

Author(s):

Vasiliki Giagka ◽

Andreas Demosthenous ◽

Nick Donaldson

Keyword(s):

Spinal Canal ◽

Electrode Arrays ◽

Active Electrode

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Electrical Stimulus Artifact Cancellation and Neural Spike Detection on Large Multi-Electrode Arrays

10.1101/089912 ◽

2016 ◽

Author(s):

Gonzalo E. Mena ◽

Lauren E. Grosberg ◽

Sasidhar Madugula ◽

Paweł Hottowy ◽

Alan Litke ◽

...

Keyword(s):

Electrical Stimulation ◽

High Resolution ◽

Action Potentials ◽

Process Model ◽

Error Rates ◽

Neural Interfaces ◽

Spike Sorting ◽

Electrode Arrays ◽

Retinal Prostheses ◽

Sorting Process

AbstractSimultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these measurements is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is greatly complicated by electrical stimulation artifacts across the array, which can exhibit complex and nonlinear waveforms, and overlap temporarily with evoked spikes. Here we develop a scalable algorithm based on a structured Gaussian Process model to estimate the artifact and identify evoked spikes. The effectiveness of our methods is demonstrated in both real and simulated 512-electrode recordings in the peripheral primate retina with single-electrode and several types of multi-electrode stimulation. We establish small error rates in the identification of evoked spikes, with a computational complexity that is compatible with real-time data analysis. This technology may be helpful in the design of future high-resolution sensory prostheses based on tailored stimulation (e.g., retinal prostheses), and for closed-loop neural stimulation at a much larger scale than currently possible.Author SummarySimultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, interpreting these recordings is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is largely stymied by electrical stimulation artifacts across the array, which are typically larger than the signals of interest. We develop a novel computational framework to estimate and subtract away this contaminating artifact, enabling the large-scale analysis of responses of possibly hundreds of cells to tailored stimulation. Importantly, we suggest that this technology may also be helpful for the development of future high-resolution neural prosthetic devices (e.g., retinal prostheses).

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An automated method for precise axon reconstruction from recordings of high-density micro-electrode arrays

10.1101/2021.06.12.448051 ◽

2021 ◽

Author(s):

Alessio Paolo Buccino ◽

Xinyue Yuan ◽

Vishalini Emmenegger ◽

Xiaohan Xue ◽

Tobias Gaenswein ◽

...

Keyword(s):

Action Potential ◽

Action Potentials ◽

Electrical Potential ◽

Simulated Data ◽

Signal Propagation ◽

High Density ◽

Electrode Arrays ◽

Action Potential Propagation ◽

Automated Method ◽

Propagation Velocities

Neurons communicate with each other by sending action potentials through their axons. The velocity of axonal signal propagation describes how fast electrical action potentials can travel, and can be affected in a human brain by several pathologies, including multiple sclerosis, traumatic brain injury and channelopathies. High-density microelectrode arrays (HD-MEAs) provide unprecedented spatio-temporal resolution to extracellularly record neural electrical activity. The high density of the recording electrodes enables to image the activity of individual neurons down to subcellular resolution, which includes the propagation of axonal signals. However, axon reconstruction, to date, mainly relies on a manual approach to select the electrodes and channels that seemingly record the signals along a specific axon, while an automated approach to track multiple axonal branches in extracellular action-potential recordings is still missing. In this article, we propose a fully automated approach to reconstruct axons from extracellular electrical-potential landscapes, so-called "electrical footprints" of neurons. After an initial electrode and channel selection, the proposed method first constructs a graph, based on the voltage signal amplitudes and latencies. Then, the graph is interrogated to extract possible axonal branches. Finally, the axonal branches are pruned and axonal action-potential propagation velocities are computed. We first validate our method using simulated data from detailed reconstructions of neurons, showing that our approach is capable of accurately reconstructing axonal branches. We then apply the reconstruction algorithm to experimental recordings of HD-MEAs and show that it can be used to determine axonal morphologies and signal-propagation velocities at high throughput. We introduce a fully automated method to reconstruct axonal branches and estimate axonal action-potential propagation velocities using HD-MEA recordings. Our method yields highly reliable and reproducible velocity estimations, which constitute an important electrophysiological feature of neuronal preparations.

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Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation

International Journal of Molecular Sciences ◽

10.3390/ijms23010351 ◽

2021 ◽

Vol 23 (1) ◽

pp. 351

Author(s):

Jae Sik Kim ◽

Seong Woo Choi ◽

Yun-Gwi Park ◽

Sung Joon Kim ◽

Chang Heon Choi ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Field Potential ◽

High Dose ◽

Acute Effects ◽

Electrode Arrays ◽

Compensatory Mechanisms ◽

Active Electrode ◽

Continuous Increase ◽

Human Cardiomyocytes ◽

Dose Irradiation

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.

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Characteristics of sodium currents in rat geniculate ganglion neurons

Journal of Neurophysiology ◽

10.1152/jn.00369.2011 ◽

2011 ◽

Vol 106 (6) ◽

pp. 2982-2991 ◽

Cited By ~ 5

Author(s):

Shiro Nakamura ◽

Robert M. Bradley

Keyword(s):

Action Potentials ◽

Receptive Fields ◽

Sensory Information ◽

Geniculate Ganglion ◽

Chorda Tympani ◽

Action Potential Generation ◽

Potential Generation ◽

Cell Recording ◽

Ganglion Neurons

Geniculate ganglion (GG) cell bodies of chorda tympani (CT), greater superficial petrosal (GSP), and posterior auricular (PA) nerves transmit orofacial sensory information to the rostral nucleus of the solitary tract. We have used whole cell recording to investigate the characteristics of the Na+ channels in isolated Fluorogold-labeled GG neurons that innervate different peripheral receptive fields. GG neurons expressed two classes of Na+ channels, TTX sensitive (TTX-S) and TTX resistant (TTX-R). The majority of GG neurons expressed TTX-R currents of different amplitudes. TTX-R currents were relatively small in 60% of the neurons but were large in 12% of the sampled population. In a further 28% of the neurons, TTX completely abolished all Na+ currents. Application of TTX completely inhibited action potential generation in all CT and PA neurons but had little effect on the generation of action potentials in 40% of GSP neurons. Most CT, GSP, and PA neurons stained positively with IB4, and 27% of the GSP neurons were capsaicin sensitive. The majority of IB4-positive GSP neurons with large TTX-R Na+ currents responded to capsaicin, whereas IB4-positive GSP neurons with small TTX-R Na+ currents were capsaicin insensitive. These data demonstrate the heterogeneity of GG neurons and indicate the existence of a subset of GSP neurons sensitive to capsaicin, usually associated with nociceptors. Since there are no reports of nociceptors in the GSP receptive field, the role of these capsaicin-sensitive neurons is not clear.

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Local interneurons define functionally distinct regions within lobster olfactory glomeruli

Journal of Experimental Biology ◽

10.1242/jeb.200.6.989 ◽

1997 ◽

Vol 200 (6) ◽

pp. 989-1001

Author(s):

M Wachowiak ◽

C Diebel ◽

B Ache

Keyword(s):

Action Potentials ◽

Spiny Lobster ◽

Olfactory Nerve ◽

Distinct Pattern ◽

Type I ◽

Type Ii ◽

Type Iv ◽

Olfactory Glomeruli ◽

Cell Recording ◽

Different Response

Whole-cell recording coupled with biocytin injection revealed four types of interneurons intrinsic to the olfactory lobe (OL) of the spiny lobster Panulirus argus. Each type of neuron had a distinct pattern of arborization within the three anatomically defined regions of OL glomeruli (cap, subcap and base). Type I interneurons innervated all three regions, while types II, III and IV branched only in the cap, subcap and base, respectively. Type I interneurons responded to electrical stimulation of the antennular (olfactory) nerve with a burst of 120 action potentials and a 110 s depolarization. Type II (cap) interneurons responded to the same input with a burst of 13 action potentials followed by a shorter hyperpolarization. Type III (subcap) interneurons responded with a burst of 16 action potentials followed by a delayed, 0.54 s depolarization. Type IV (base) interneurons responded with a brief depolarization or a burst of 13 action potentials followed by a 1 s hyperpolarization. The regionalized arborization and the different response properties of the type II, III and IV interneurons strongly imply that lobster olfactory glomeruli contain functionally distinct regions, a feature that should be useful in understanding the multiple synaptic pathways involved in processing olfactory input.

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