Editing trains of action potentials from multi-electrode arrays

2004 ◽  
Vol 134 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Richard B. Stein ◽  
Douglas J. Weber
2017 ◽  
Author(s):  
Daniel C. Bridges ◽  
Kenneth R. Tovar ◽  
Bian Wu ◽  
Paul K. Hansma ◽  
Kenneth S. Kosik

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.


2008 ◽  
Vol 99 (3) ◽  
pp. 1545-1553 ◽  
Author(s):  
Jonathan A. N. Fisher ◽  
Jonathan R. Barchi ◽  
Cristin G. Welle ◽  
Gi-Ho Kim ◽  
Paul Kosterin ◽  
...  

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.


2016 ◽  
Author(s):  
Gonzalo E. Mena ◽  
Lauren E. Grosberg ◽  
Sasidhar Madugula ◽  
Paweł Hottowy ◽  
Alan Litke ◽  
...  

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).


2021 ◽  
Author(s):  
Alessio Paolo Buccino ◽  
Xinyue Yuan ◽  
Vishalini Emmenegger ◽  
Xiaohan Xue ◽  
Tobias Gaenswein ◽  
...  

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.


2003 ◽  
Vol 13 (09) ◽  
pp. 2513-2535 ◽  
Author(s):  
Walter J. Freeman

Domains of cooperative neural activity called "wave packets" have been discovered in the visual, auditory, and somatomotor cortices of rabbits that were trained to discriminate conditioned stimuli in these modalities. Each domain forms by a first order state transition, which strongly resembles a phase transition from vapor to liquid. In this view, raw sense data injected into cortex by sensory axons drive cortical action potentials in swarms like water molecules in steam. The increased activity destabilizes the cortex. Within 3 to 7 milliseconds of transition onset, the activity binds together into a state resembling a scintillating rain drop, which lasts ~80 to 100 milliseconds, then dissolves. Wave packets form at rates of 2 to 7/second in all sensory areas, overlapping in space and time. Results of sensory information processing are seen in spatial patterns of amplitude modulation (AM) of wave packets with carrier waves in the gamma range (20 to 80 Hz in rabbits). The AM patterns correspond to categories of CSs that the rabbits can discriminate. The patterns are found in electroencephalographic (EEG) potentials generated by dendrites and recorded with high-density electrode arrays. The state transitions by which AM patterns form are manifested in the spatial pattern of phase modulation (PM), which have the radial symmetry of a cone. The apex of a PM cone marks the site of nucleation of an AM pattern. The phase gradient gives a soft boundary condition, where the axonal delay in spread gives sufficient phase dispersion to reach the half-power level. The size of the wave packets (10 to 30 mm in diameter in rabbits) is determined largely by the conduction velocities of intracortical axons through which the neural cooperation is maintained. The findings show that significant cortical activity takes the form of mesoscopic interactions of millions of neurons in broad areas of cortex, which are more clearly detected in graded dendritic potentials than in action potentials. The distinction is analogous to the difference between statistical mechanical and thermodynamic descriptions of particle behavior. Both types of neural activity show spatial and temporal discontinuities but at distinctive scales of microns and msec versus mm and tenths of a second. The aim of measurement here is to establish the wave packet as the information carrier at the mesoscopic level in brain dynamics, comparable to the role of the action potential as the information carrier at the microscopic level in neuron dynamics.


2018 ◽  
Author(s):  
Xiaoxuan Jia ◽  
Josh Siegle ◽  
Corbett Bennett ◽  
Sam Gale ◽  
Daniel R Denman ◽  
...  

AbstractDifferent neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morpho-electric properties of neurons measured on spatially dense electrode arrays might be useful for distinguishing neuron types. Here we used Neuropixels probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multi-channel compared to single-channel waveforms. In visual cortex, waveform clustering identified the canonical regular spiking (RS) and fast spiking (FS) classes, but also uncovered a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation.


2017 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Daniel C. Bridges ◽  
Bian Wu ◽  
Connor Randall ◽  
Morgane Audouard ◽  
...  

AbstractThe small caliber of central nervous system (CNS) axons makes routine study of axonal physiology relatively difficult. However, while recording extracellular action potentials from neurons cultured on planer multi-electrode arrays (MEAs) we found activity among groups of electrodes consistent with action potential propagation in single neurons. Action potential propagation was evident as widespread, repetitive cooccurrence of extracellular action potentials (eAPs) among groups of electrodes. These eAPs occurred with invariant sequences and inter-electrode latencies that were consistent with reported measures of action potential propagation in unmyelinated axons. Within co-active electrode groups, the inter-electrode eAP latencies were temperature sensitive, as expected for action potential propagation. Our data are consistent with these signals primarily reflecting axonal action potential propagation, from axons with a high density of voltage-gated sodium channels. Repeated codetection of eAPs by multiple electrodes confirmed these eAPs are from individual neurons and averaging these eAPs revealed sub-threshold events at other electrodes. The sequence of electrodes at which eAPs co-occur uniquely identifies these neurons, allowing us to monitor spiking of single identified neurons within neuronal ensembles. We recorded dynamic changes in single axon physiology such as simultaneous increases and decreases in excitability in different portions of single axonal arbors over several hours. Over several weeks, we measured changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. We recorded action potential propagation signals in human induced pluripotent stem cell-derived neurons which could thus be used to study axonal physiology in human disease models.Significance StatementStudying the physiology of central nervous system axons is limited by the technical challenges of recording from axons with pairs of patch or extracellular electrodes at two places along single axons. We studied action potential propagation in single axonal arbors with extracellular recording with multi-electrode arrays. These recordings were non-invasive and were done from several sites of small caliber axons and branches. Unlike conventional extracellular recording, we unambiguously identified and labelled the neuronal source of propagating action potentials. We manipulated and quantified action potential propagation and found a surprisingly high density of axonal voltage-gated sodium channels. Our experiments also demonstrate that the excitability of different portions of axonal arbors can be independently regulated on time scales from hours to weeks.


Lab on a Chip ◽  
2012 ◽  
Vol 12 (21) ◽  
pp. 4397 ◽  
Author(s):  
Dries Braeken ◽  
Danny Jans ◽  
Roeland Huys ◽  
Andim Stassen ◽  
Nadine Collaert ◽  
...  

2019 ◽  
Vol 24 (6) ◽  
pp. 299-308 ◽  
Author(s):  
Pernilla Videhult Pierre ◽  
Martin Eklöf ◽  
Henrik Smeds ◽  
Filip Asp

Introduction: Precurved cochlear implant (CI) electrode arrays were developed in an attempt to improve the auditory outcome of cochlear implantation, which varies greatly. The recent CI532 (Cochlear Corp., Sydney, Australia) may offer further advantages as its electrode array is thinner than previous precurved CI electrode arrays. The aims here were to investigate 1-year postoperative speech recognition, intraoperative electrically evoked compound action potentials (ECAPs), and their possible relation in patients implanted with a CI532 or its predecessor CI512. Methods: A retrospective analysis of data from 63 patients subjected to cochlear implantation at the Karolinska University Hospital, Sweden, was performed. Speech recognition of the implanted ear was evaluated using phonemically balanced monosyllabic Swedish words at 65 dB SPL. ECAPs were evaluated using the intraoperative ECAP threshold across ≥8 electrodes generated by the automated neural response telemetry of the CI. Results: The median aided speech recognition score (SRS) 1 year after implantation was 52% (quartile 1 = 40%, quartile 3 = 60%, n = 63) and did not differ statistically significantly between patients with CI512 (n = 38) and CI532 (n = 25). The mean ECAP threshold was 188 CL (current level; SD = 15 CL, n = 54) intraoperatively and did not differ statistically significantly between patients with CI512 (n = 32) and CI532 (n = 22), but the threshold for each electrode varied more between patients with a CI512 (p < 0.0001). A higher mean ECAP threshold was associated with a worse SRS (Spearman’s ρ = –0.46, p = 0.0004, n = 54). The association remained among those with a CI512 (Spearman’s ρ = –0.62, p = 0.0001, n = 32) when stratified by CI electrode array. Conclusion: No statistically significant difference in speech recognition 1 year after cochlear implantation or in mean threshold of ECAP intraoperatively was found between patients with a CI512 and the more recent, slim CI532, but the ECAP thresholds varied more between those with a CI512. A statistically significant association between SRS and mean ECAP threshold was found, but stratified analysis suggests that the association may be true only for patients with a CI512.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
C J Dykstra-Aiello ◽  
K Koh ◽  
J Nguyen ◽  
J M Krueger

Abstract Introduction Tumor necrosis factor (TNF) has sleep regulatory roles. Neuronal action potentials enhance TNF expression. Neuron/glia co-cultures exhibit more intense local sleep-like states after TNF administration in vitro. Both TNF and TNF receptors (Rs) are produced as transmembrane (tm) proteins that can subsequently be cleaved to produce soluble (s) forms. With immunocytes, sTNFR can bind tmTNF and induce reverse signaling within the cell expressing the tmTNF. This is opposite of conventional signaling induced by soluble ligands (e.g. sTNF) binding to transmembrane receptors. Having previously shown sleep inhibition after sTNFR administration in vivo, we hypothesized that tmTNF-sTNFR binding would induce wake-like states in vitro through reverse signaling. Methods Somatosensory cortical neurons/glia, from wildtype (WT) mice and mice lacking either TNF (TNF-KO) or both TNFRs (TNFR-KO), were co-cultured on multi-electrode arrays. Daily one-hour recordings were taken consecutively on incubation days 4 - 13 for development analyses. On day 14, a one-hour baseline was recorded prior to treatment with sTNFR (0.0 ng/μL-120 ng/μL). Immediately after treatment, recordings resumed for one hour. Synchronization of electrical activity (SYN), action potentials, slow wave power (SWP; 0.25–3.75 Hz), and burstiness index (measures used to define sleep in vivo) were used to characterize the ontological emergence of these electrophysiological properties and sTNFR-induced changes in vitro. Results Development rates were reduced in TNF-KO cells and increased in TNFR-KO cells relative to each other and to WT mice. Additionally, after sTNFR treatments, cells from TNFR-KO mice, which still express TNF, exhibited dose-dependent decreased SYN and SWP, indicative of a wake-like state. In contrast, cells from TNF-KO mice lacked a response to sTNFR treatment. Conclusion To our knowledge, this is the first demonstration of reverse TNF signaling with respect to sleep/wake states. As such, it provides a new way of viewing state regulation and associated potential clinical applications. Support This work was supported by grant NS096250 awarded to JK by NIH/NINDS.


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