scholarly journals Recording action potential propagation in single axons using multi-electrode arrays

2017 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Daniel C. Bridges ◽  
Bian Wu ◽  
Connor Randall ◽  
Morgane Audouard ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Extracellular Recording ◽  
Electrode Arrays ◽  
Action Potential Propagation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Axonal Arbors

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.

Voltage-gated sodium channels and pain

e-Neuroforum ◽  
2017 ◽  
Vol 23 (3) ◽  
Author(s):  
Carla Nau ◽  
Enrico Leipold
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sodium Channels ◽  
Action Potentials ◽  
Afferent Pathways ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
The Central Nervous System

AbstractPainful stimuli are detected by specialized neurons, nociceptors, and are translated into action potentials, that are conducted along afferent pathways into the central nervous system, where they are conceived as pain. Voltage-gated sodium channels (Na

scholarly journals Action potential propagation recorded from single axonal arbors using multielectrode arrays

2018 ◽  
Vol 120 (1) ◽  
pp. 306-320 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Daniel C. Bridges ◽  
Bian Wu ◽  
Connor Randall ◽  
Morgane Audouard ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Detection Threshold ◽  
Physiological Data ◽  
Low Density ◽  
Multielectrode Arrays ◽  
Action Potential Propagation ◽  
Voltage Gated ◽  
Axonal Arbors

We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multielectrode arrays (MEAs). The invariant sequences of eAPs among coactive electrode groups, repeated co-occurrences, and short interelectrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP codetection by multiple electrodes was widespread in all our data records. Codetection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among coactive electrodes “fingerprints” neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the noninvasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in interelectrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low-density MEAs. However, repeated eAP co-occurrences lead to oversampling spikes from single neurons and thus can confound traditional spike-train analysis. NEW & NOTEWORTHY We studied action potential propagation in single axons using low-density multielectrode arrays. We unambiguously identified the neuronal sources of propagating action potentials and recorded extracellular action potentials from several positions within single axonal arbors. We found a surprisingly high density of axonal voltage-gated sodium channels responsible for a high propagation safety factor. Our experiments also demonstrate that excitability in different segments of single axons is regulated independently on timescales from hours to weeks.

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.

scholarly journals Voltage-gated sodium channels in neocortical pyramidal neurons display Cole-Moore activation kinetics

2017 ◽  
Author(s):  
Mara Almog ◽  
Tal Barkai ◽  
Angelika Lampert ◽  
Alon Korngreen
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Gating Mechanism ◽  
Cortical Pyramidal Neurons

AbstractExploring the properties of action potentials is a crucial step towards a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. Most models of voltage-gated sodium channels assume it obeys a concerted Hodgkin and Huxley kinetic gating scheme. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. This may have key implications for the role of sodium channels in synaptic integration and action potential generation.

scholarly journals Action Potentials and Na+ voltage-gated ion channels in Placozoa

2020 ◽  
Author(s):  
Daria Y. Romanova ◽  
Ivan V. Smirnov ◽  
Mikhail A. Nikitin ◽  
Andrea B. Kohn ◽  
Alisa I. Borman ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Parallel Evolution ◽  
Cell Types ◽  
List Type ◽  
Behavioral Integration ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Invertebrate Animal ◽  
Sodium Dependent

AbstractPlacozoa are small disc-shaped animals, representing the simplest known, possibly ancestral, organization of free-living animals. With only six morphological distinct cell types, without any recognized neurons or muscle, placozoans exhibit fast effector reactions and complex behaviors. However, little is known about electrogenic mechanisms in these animals. Here, we showed the presence of rapid action potentials in four species of placozoans (Trichoplax adhaerens [H1 haplotype], Trichoplax sp.[H2], Hoilungia hongkongensis [H13], and Hoilungia sp. [H4]). These action potentials are sodium-dependent and can be inducible. The molecular analysis suggests the presence of 5-7 different types of voltage-gated sodium channels, which showed substantial evolutionary radiation compared to many other metazoans. Such unexpected diversity of sodium channels in early-branched animal lineages reflect both duplication events and parallel evolution of unique behavioral integration in these nerveless animals.HighlightsPlacozoans are the simplest known animals without recognized neurons and musclesWith only six morphological cell types, placozoans showed complex & rapid behaviorsSodium-dependent action potentials have been discovered in intact animalsVoltage-gated sodium channels (Nav) in Placozoa support a rapid behavioral integrationPlacozoans have more Nav channels that any studied invertebrate animal so farDiversification of Nav-channels highlight the unique evolution of these nerveless animals

scholarly journals Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain

Processes ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 680 ◽  
Author(s):  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Action Potential ◽  
Sodium Channels ◽  
Sodium Current ◽  
Voltage Response ◽  
Treatment Schedule ◽  
Voltage Gated ◽  
Peripheral Neurons ◽  
Voltage Gated Sodium Channels ◽  
Current Voltage

Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxaliplatin on sodium channels of peripheral neurons have been included. Its effects on the duration of the action potential, peak of the sodium current, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) are discussed.

scholarly journals Conserved Expression of Nav1.7 and Nav1.8 Contribute to the Spontaneous and Thermally Evoked Excitability in IL-6 and NGF-Sensitized Adult Dorsal Root Ganglion Neurons In Vitro

2020 ◽  
Vol 7 (2) ◽  
pp. 44
Author(s):  
Rahul R. Atmaramani ◽  
Bryan J. Black ◽  
June Bryan de la Peña ◽  
Zachary T. Campbell ◽  
Joseph J. Pancrazio
Keyword(s):  
Sodium Channels ◽  
Sensory Neurons ◽  
Inflammatory Pain ◽  
Dorsal Root Ganglion Neurons ◽  
Electrode Arrays ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Ganglion Neurons

Sensory neurons respond to noxious stimuli by relaying information from the periphery to the central nervous system via action potentials driven by voltage-gated sodium channels, specifically Nav1.7 and Nav1.8. These channels play a key role in the manifestation of inflammatory pain. The ability to screen compounds that modulate voltage-gated sodium channels using cell-based assays assumes that key channels present in vivo is maintained in vitro. Prior electrophysiological work in vitro utilized acutely dissociated tissues, however, maintaining this preparation for long periods is difficult. A potential alternative involves multi-electrode arrays which permit long-term measurements of neural spike activity and are well suited for assessing persistent sensitization consistent with chronic pain. Here, we demonstrate that the addition of two inflammatory mediators associated with chronic inflammatory pain, nerve growth factor (NGF) and interleukin-6 (IL-6), to adult DRG neurons increases their firing rates on multi-electrode arrays in vitro. Nav1.7 and Nav1.8 proteins are readily detected in cultured neurons and contribute to evoked activity. The blockade of both Nav1.7 and Nav1.8, has a profound impact on thermally evoked firing after treatment with IL-6 and NGF. This work underscores the utility of multi-electrode arrays for pharmacological studies of sensory neurons and may facilitate the discovery and mechanistic analyses of anti-nociceptive compounds.

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