scholarly journals High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification

2019 ◽  
Vol 121 (5) ◽  
pp. 1831-1847 ◽  
Author(s):  
Xiaoxuan Jia ◽  
Joshua H. Siegle ◽  
Corbett Bennett ◽  
Samuel D. Gale ◽  
Daniel J. Denman ◽  
...  
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Brain Network ◽  
High Density ◽  
Waveform Analysis ◽  
Cell Type ◽  
Electrode Arrays

Different 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. Morphoelectrical properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. We used high-density silicon 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 multichannel compared with single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular-spiking (RS) and fast-spiking (FS) classes but also indicated 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. NEW & NOTEWORTHY It is challenging to identify neuron types with extracellular electrophysiology in vivo. We show that spatiotemporal action potentials measured on high-density electrode arrays can capture cell type-specific morphoelectrical properties, allowing classification of neurons across brain structures and within the cortex. Moreover, backpropagating action potentials are reliably detected in vivo from subpopulations of cortical and hippocampal neurons. Together, these results enhance the utility of dense extracellular electrophysiology for cell-type interrogation of brain network function.

scholarly journals High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification

2018 ◽  
Author(s):  
Xiaoxuan Jia ◽  
Josh Siegle ◽  
Corbett Bennett ◽  
Sam Gale ◽  
Daniel R Denman ◽  
...  
Keyword(s):  
Brain Function ◽  
Action Potentials ◽  
Single Channel ◽  
Brain Regions ◽  
High Density ◽  
Waveform Analysis ◽  
Electrode Arrays ◽  
Fast Spiking ◽  
Subcortical Regions

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.

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

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.

Polytrodes: High-Density Silicon Electrode Arrays for Large-Scale Multiunit Recording

2005 ◽  
Vol 93 (5) ◽  
pp. 2987-3000 ◽  
Author(s):  
Timothy J. Blanche ◽  
Martin A. Spacek ◽  
Jamille F. Hetke ◽  
Nicholas V. Swindale
Keyword(s):  
Large Scale ◽  
High Density ◽  
Clustering Methods ◽  
Electrode Arrays ◽  
Large Numbers ◽  
High Bandwidth ◽  
Electrode Positioning ◽  
Multiunit Recording ◽  
Silicon Based

We developed a variety of 54-channel high-density silicon electrode arrays (polytrodes) designed to record from large numbers of neurons spanning millimeters of brain. In cat visual cortex, it was possible to make simultaneous recordings from >100 well-isolated neurons. Using standard clustering methods, polytrodes provide a quality of single-unit isolation that surpasses that attainable with tetrodes. Guidelines for successful in vivo recording and precise electrode positioning are described. We also describe a high-bandwidth continuous data-acquisition system designed specifically for polytrodes and an automated impedance meter for testing polytrode site integrity. Despite having smaller interconnect pitches than earlier silicon-based electrodes of this type, these polytrodes have negligible channel crosstalk, comparable reliability, and low site impedances and are capable of making high-fidelity multiunit recordings with minimal tissue damage. The relatively benign nature of planar electrode arrays is evident both histologically and in experiments where the polytrode was repeatedly advanced and retracted hundreds of microns over periods of many hours. It was possible to maintain stable recordings from active neurons adjacent to the polytrode without change in their absolute positions, neurophysiological or receptive field properties.

scholarly journals 0017 Transmembrane TNF- Soluble TNF Receptor Reverse Signal to Induce a Wake-Like State in Vitro

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
C J Dykstra-Aiello ◽  
K Koh ◽  
J Nguyen ◽  
J M Krueger
Keyword(s):  
Cortical Neurons ◽  
Action Potentials ◽  
State Regulation ◽  
Electrode Arrays ◽  
Electrophysiological Properties ◽  
Reverse Signaling ◽  
Soluble Tnf Receptor ◽  
Induced Changes

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.

scholarly journals Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

2015 ◽  
Vol 112 (32) ◽  
pp. E4485-E4494 ◽  
Author(s):  
Kristal R. Tucker ◽  
Ethan R. Block ◽  
Edwin S. Levitan
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
D2 Receptor ◽  
Brain Slices ◽  
Ph Gradients ◽  
Dopaminergic Transmission ◽  
Two Photon Microscopy ◽  
Two Photon

Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

scholarly journals An Algorithm for Tracking the Position and Velocity of Multiple Neuronal Signals Using Implantable Microelectrodes In Vivo

Micromachines ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1346
Author(s):  
Lionel M. Broche ◽  
Karla D. Bustamante ◽  
Michael Pycraft Hughes
Keyword(s):  
Nervous System ◽  
Action Potential ◽  
Small Groups ◽  
Action Potentials ◽  
Interconnected Network ◽  
Electrode Arrays ◽  
Action Potential Propagation ◽  
Physical Form

Increasingly complex multi-electrode arrays for the study of neurons both in vitro and in vivo have been developed with the aim of tracking the conduction of neural action potentials across a complex interconnected network. This is usually performed through the use of electrodes to record from single or small groups of microelectrodes, and using only one electrode to monitor an action potential at any given time. More complex high-density electrode structures (with thousands of electrodes or more) capable of tracking action potential propagation have been developed but are not widely available. We have developed an algorithm taking data from clusters of electrodes positioned such that action potentials are detected by multiple sites, and using this to detect the location and velocity of action potentials from multiple neurons. The system has been tested by analyzing recordings from probes implanted into the locust nervous system, where recorded positions and velocities correlate well with the known physical form of the nerve.

Motor Unit Tracking Using High Density Surface Electromyography (HDsEMG)

2015 ◽  
Vol 54 (03) ◽  
pp. 221-226 ◽  
Author(s):  
B. T. H. M. Sleutjes ◽  
M. De Vos ◽  
J. H. Blok ◽  
I. Montfoort ◽  
B. Mijović ◽  
...  
Keyword(s):  
Motor Unit ◽  
Action Potentials ◽  
Motor Units ◽  
Surface Emg ◽  
High Density ◽  
Electrode Arrays ◽  
Motor Unit Action Potentials ◽  
Motor Unit Action ◽  
Angular Displacements ◽  
Unit Action

SummaryIntroduction: This article is part of the Focus Theme of Methods of Information in Medicine on “Biosignal Interpretation: Advanced Methods for Neural Signals and Images”.Objectives: The study discusses a technique to automatically correct for effects of electrode grid displacement across serial surface EMG measurements with high-density electrode arrays (HDsEMG). The goal is to match motor unit signatures from subsequent measurements and by this, achieve automated motor unit tracking.Methods: Test recordings of voluntary muscle contractions using HDsEMG were performed on three healthy individuals. Electrode grid displacements were mimicked in repeated recordings while measuring the exact position of the grid. A concept of accounting for translational and rotational displacements by making the projection of the recorded motor unit action potentials is first introduced. Then, this concept was tested for the performed measurements attempting the automated matching of the similar motor unit action potentials across different trials.Results: The ability to perform automated correction (projection) of the isolated motor unit action potentials was first shown using large angular displacements. Then, for accidental (small) displacements of the recording grid, the ability to automatically track motor units across different measurement trials was shown. It was possible to track 10 –15% of identified motor units.Conclusions: This proof of concept study demonstrates an automated correction allowing the identification of an increased number of same motor unit action potentials across different measurements. By this, great potential is demonstrated for assisting motor unit tracking studies, indicating that otherwise electrode displacements cannot always be precisely described.

scholarly journals Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons

2018 ◽  
Vol 47 (1) ◽  
pp. 330-343 ◽  
Author(s):  
Chin-Wei Huang ◽  
Kao-Min Lin ◽  
Te-Yu Hung ◽  
Yao-Chung Chuang ◽  
Sheng-Nan Wu
Keyword(s):  
Hippocampal Neurons ◽  
Time Course ◽  
Single Channel ◽  
Inactivation Kinetics ◽  
Ion Currents ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Inactivation Curve ◽  
End Plate

Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

scholarly journals Non-parametric physiological classification of retinal ganglion cells in the mouse retina

2018 ◽  
Author(s):  
Jonathan Jouty ◽  
Gerrit Hilgen ◽  
Evelyne Sernagor ◽  
Matthias H. Hennig
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Large Scale ◽  
Distance Measure ◽  
Ganglion Cells ◽  
High Density ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Electrode Arrays

Retinal ganglion cells, the sole output neurons of the retina, exhibit surprising diversity. A recent study reported over 30 distinct types in the mouse retina, indicating that the processing of visual information is highly parallelised in the brain. The advent of high density multi-electrode arrays now enables recording from many hundreds to thousands of neurons from a single retina. Here we describe a method for the automatic classification of large-scale retinal recordings using a simple stimulus paradigm and a spike train distance measure as a clustering metric. We evaluate our approach using synthetic spike trains, and demonstrate that major known cell types are identified in high-density recording sessions from the mouse retina with around 1000 retinal ganglion cells. A comparison across different retinas reveals substantial variability between preparations, suggesting pooling data across retinas should be approached with caution. As a parameter-free method, our approach is broadly applicable for cellular physiological classification in all sensory modalities.

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