scholarly journals Neuronal firing and waveform alterations through ictal recruitment in humans

2020 ◽  
Author(s):  
Edward M. Merricks ◽  
Elliot H. Smith ◽  
Ronald G. Emerson ◽  
Lisa M. Bateman ◽  
Guy M. McKhann ◽  
...  
Keyword(s):  
Action Potential ◽  
Template Matching ◽  
Animal Studies ◽  
Microelectrode Array ◽  
Focal Epilepsy ◽  
Neuronal Firing ◽  
Single Neurons ◽  
Action Potential Waveform ◽  
Concentration Changes ◽  
Potential Waveform

AbstractClinical analyses of neuronal activity during seizures, invariably using extracellular recordings, is greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the “noise”; all three factors confound attempts to detect and classify single neurons (units). To address these analytical difficulties, we developed a novel template-matching based spike sorting method, which enabled identification of 1,239 single units in 27 patients with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing through the ictal transition, which was defined as a transient period of intense tonic firing consistent with previous descriptions of the ictal wavefront. After the ictal transition, neurons displayed increased spike duration (p < 0.001) and reduced spike amplitude (p < 0.001), in keeping with prior animal studies; units in non-recruited territories, by contrast, showed more stable waveforms. All units returned to their pre-ictal waveforms after seizure termination. Waveshape changes were stereotyped across seizures within patients. Our analyses of single neuron firing patterns, at the ictal wavefront, showed widespread intense activation, and commonly involving marked waveshape alteration. We conclude that the distinction between tissue that has been recruited to the seizure versus non-recruited territories is evident at the level of single neurons, and that increased waveform duration and decreased waveform amplitude are hallmarks of seizure invasion that could be used as defining characteristics of local recruitment.Significance StatementAnimal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proved difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude, while penumbral tissue shows stable action potentials, in keeping with the “dual territory” model of seizure dynamics.

scholarly journals A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons

2018 ◽  
Vol 119 (4) ◽  
pp. 1506-1520 ◽  
Author(s):  
David B. Jaffe ◽  
Robert Brenner
Keyword(s):  
Action Potential ◽  
Computational Model ◽  
Interspike Interval ◽  
Computational Study ◽  
Stimulus Frequency ◽  
Bk Channels ◽  
Neuronal Firing ◽  
Inward Current ◽  
Action Potential Waveform ◽  
Potential Waveform

The gain of a neuron, the number and frequency of action potentials triggered in response to a given amount of depolarizing injection, is an important behavior underlying a neuron’s function. Variations in action potential waveform can influence neuronal discharges by the differential activation of voltage- and ion-gated channels long after the end of a spike. One component of the action potential waveform, the afterhyperpolarization (AHP), is generally considered an inhibitory mechanism for limiting firing rates. In dentate gyrus granule cells (DGCs) expressing fast-gated BK channels, large fast AHPs (fAHP) are paradoxically associated with increased gain. In this article, we describe a mechanism for this behavior using a computational model. Hyperpolarization provided by the fAHP enhances activation of a dendritic inward current (a T-type Ca2+ channel is suggested) that, in turn, boosts rebound depolarization at the soma. The model suggests that the fAHP may both reduce Ca2+ channel inactivation and, counterintuitively, enhance its activation. The magnitude of the rebound depolarization, in turn, determines the activation of a subsequent, slower inward current (a persistent Na+ current is suggested) limiting the interspike interval. Simulations also show that the effect of AHP on gain is also effective for physiologically relevant stimulation; varying AHP amplitude affects interspike interval across a range of “noisy” stimulus frequency and amplitudes. The mechanism proposed suggests that small fAHPs in DGCs may contribute to their limited excitability. NEW & NOTEWORTHY The afterhyperpolarization (AHP) is canonically viewed as a major factor underlying the refractory period, serving to limit neuronal firing rate. We recently reported that enhancing the amplitude of the fast AHP (fAHP) in a relatively slowly firing neuron (vs. fast spiking neurons) expressing fast-gated BK channels augments neuronal excitability. In this computational study, we present a novel, quantitative hypothesis for how varying the amplitude of the fAHP can, paradoxically, influence a subsequent spike tens of milliseconds later.

scholarly journals Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38482 ◽  
Author(s):  
Peter Stratton ◽  
Allen Cheung ◽  
Janet Wiles ◽  
Eugene Kiyatkin ◽  
Pankaj Sah ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Waveform ◽  
Freely Behaving ◽  
Potential Waveform

scholarly journals Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

scholarly journals Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

2022 ◽  
pp. 105609
Author(s):  
Rémi Bos ◽  
Khalil Rihan ◽  
Patrice Quintana ◽  
Lara El-Bazzal ◽  
Nathalie Bernard-Marissal ◽  
...  
Keyword(s):  
Action Potential ◽  
Motor Neurons ◽  
Initial Segment ◽  
Axonal Initial Segment ◽  
Action Potential Waveform ◽  
Potential Waveform

scholarly journals Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum

2020 ◽  
Vol 10 (12) ◽  
pp. 897
Author(s):  
Tara Barron ◽  
Jun Hee Kim
Keyword(s):  
Preterm Birth ◽  
Action Potential ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Late Gestation ◽  
Cerebellar Development ◽  
Layer Width ◽  
Action Potential Waveform ◽  
Developmental Features ◽  
Potential Waveform

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

Effects of ACh and adenosine mediated by Kir3.1 and Kir3.4 on ferret ventricular cells

2002 ◽  
Vol 283 (2) ◽  
pp. H615-H630 ◽  
Author(s):  
H. Dobrzynski ◽  
N. C. Janvier ◽  
R. Leach ◽  
J. B. C. Findlay ◽  
M. R. Boyett
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Current Clamp ◽  
Inotropic Effects ◽  
Clamp Technique ◽  
Action Potential Clamp ◽  
Ventricular Cells ◽  
Action Potential Waveform ◽  
Potential Waveform ◽  
Action Potential Shortening

The inotropic effects of ACh and adenosine on ferret ventricular cells were investigated with the action potential-clamp technique. Under current clamp, both agonists resulted in action potential shortening and a decrease in contraction. Under action potential clamp, both agonists failed to decrease contraction substantially. In the absence of agonist, application of the short action potential waveform (recorded previously in the presence of agonist) also resulted in a decrease in contraction. Under action potential clamp, application of ACh resulted in a Ba2+-sensitive outward current with the characteristics of muscarinic K+ current ( I K,ACh); the presence of the muscarinic K+ channel was confirmed by PCR and immunocytochemistry. In the absence of agonist, on application of the short ACh action potential waveform, the decrease in contraction was accompanied by loss of the inward Na+/Ca2+exchange current ( I NaCa). ACh also inhibited the background inward K+ current ( I K,1). It is concluded that ACh activates I K,ACh, inhibits I K,1, and indirectly inhibits I NaCa; this results in action potential shortening, decrease in contraction, and, as a result of the inhibition of I K,1, minimum decrease in excitability.

scholarly journals Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
M. Pásek ◽  
J. Šimurda ◽  
G. Christé
Keyword(s):  
Action Potential ◽  
Transport Systems ◽  
Duration Of Action ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Before And After ◽  
Action Potential Waveform ◽  
Intracellular Ca ◽  
Tubular Membranes ◽  
Potential Waveform

The ratio of densities of Na-Ca exchanger current (INaCa) in the t-tubular and surface membranes (INaCa-ratio) computed from the values ofINaCaand membrane capacitances (Cm) measured in adult rat ventricular cardiomyocytes before and after detubulation ranges between 1.7 and 25 (potentially even 40). Variations of action potential waveform and of calcium turnover within this span of theINaCa-ratio were simulated employing previously developed model of rat ventricular cell incorporating separate description of ion transport systems in the t-tubular and surface membranes. The increase ofINaCa-ratio from 1.7 to 25 caused a prolongation of APD (duration of action potential at 90% repolarisation) by 12, 9, and 6% and an increase of peak intracellular Ca2+transient by 45, 19, and 6% at 0.1, 1, and 5 Hz, respectively. The prolonged APD resulted from the increase ofINaCadue to the exposure of a larger fraction of Na-Ca exchangers to higher Ca2+transients under the t-tubular membrane. The accompanying rise of Ca2+transient was a consequence of a higher Ca2+load in sarcoplasmic reticulum induced by the increased Ca2+cycling between the surface and t-tubular membranes. However, the reason for large differences in theINaCa-ratio assessed from measurements in adult rat cardiomyocytes remains to be explained.

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