Jittery Trains Induced by Synaptic-Like Currents in Cerebellar Inhibitory Interneurons

2002 ◽  
Vol 87 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Puah Mann-Metzer ◽  
Yosef Yarom
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Spike Timing ◽  
Temporal Coding ◽  
Parallel Fiber ◽  
Delayed Rectifier ◽  
Inhibitory Interneurons ◽  
Synaptic Current ◽  
Large Variability ◽  
Membrane Hyperpolarization

Cerebellar inhibitory interneurons respond to parallel fiber input with a characteristic train of action potentials. Here we show that the characteristics of these trains reflect the intrinsic properties of the interneurons. In in vitro cerebellar slices, the response of these neurons to synaptic-like current resembles their in vivo response to parallel fiber input—a train of action potentials characterized by a gradual increase in interspike interval and spike amplitude. A large variability in spike timing, or jitter, was observed, the last action potential emerging from a slow depolarizing wave that lasted beyond the synaptic current and was prevented by either TTX or membrane hyperpolarization. While response duration was weakly dependent on current intensity, the variability of the overall duration was closely related to the variability of the timing of the last action potential. Blocking the Ca2+ currents or partial blockade of the delayed rectifier (TEA 2 mM) decreased the excitability, leading to a decrease in the duration and variability of the response and increasing its dependence on stimulus intensity. Increased duration and variability was observed in the presence of Cs+ ions (5 mM) that blocked an h-like current. We conclude that a persistent Na+ current governs the duration of the response, whereas the synaptic current and the spiking mechanism shape its pattern. The large variability between trials is due to the stochastic nature of the persistent Na+ current. Thus unless precise timing is achieved by a network of interconnected neurons, these results vote against temporal coding as a player in the cerebellar computational processing.

Activity-Dependent Modulation of Axonal Excitability in Unmyelinated Peripheral Rat Nerve Fibers by the 5-HT(3) Serotonin Receptor

2006 ◽  
Vol 96 (6) ◽  
pp. 2963-2971 ◽  
Author(s):  
Philip M. Lang ◽  
Gila Moalem-Taylor ◽  
David J. Tracey ◽  
Hugh Bostock ◽  
Peter Grafe
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Serotonin Receptor ◽  
Nerve Fibers ◽  
Nerve Trunk ◽  
Axonal Membrane ◽  
Membrane Hyperpolarization ◽  
Axonal Excitability ◽  
Activity Dependent

Activity-dependent fluctuations in axonal excitability and changes in interspike intervals modify the conduction of trains of action potentials in unmyelinated peripheral nerve fibers. During inflammation of a nerve trunk, long stretches of axons are exposed to inflammatory mediators such as 5-hydroxytryptamine [5-HT]. In the present study, we have tested the effects of m-chlorophenylbiguanide (mCPBG), an agonist at the 5-HT(3) serotonin receptor, on activity- and potential-dependent variations in membrane threshold and conduction velocity of unmyelinated C-fiber axons of isolated rat sural nerve segments. The increase in axonal excitability during application of mCPBG was much stronger at higher frequencies of action potentials and/or during axonal membrane hyperpolarization. The effects on the postspike recovery cycle also depended on the rate of stimulation. At an action potential frequency of 1 Hz or in hyperpolarized axons, mCPBG produced a loss of superexcitability. In contrast, at 0.33 Hz, a small increase in the postspike subexcitability was observed. Similar effects on excitability changes were found when latency instead of threshold was recorded, but only at higher action potential frequencies: at 1.8 Hz, mCPBG increased conduction velocity and reduced postspike supernormality. The latter effect would increase the interspike interval if pairs of action potentials were conducted along several cm in an inflamed nerve trunk. These data indicate that activation of axonal 5-HT(3) receptors not only enhances membrane excitability but also modulates action potential trains in unmyelinated, including nociceptive, nerve fibers at high impulse rates.

scholarly journals Modeling noise mechanisms in neuronal synaptic transmission

2017 ◽  
Author(s):  
Abhyudai Singh
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potentials ◽  
Spike Timing ◽  
Critical Threshold ◽  
Model Parameters ◽  
Postsynaptic Neuron ◽  
Presynaptic Neuron ◽  
Vesicle Release ◽  
First Time

In the nervous system, communication occurs via synaptic transmission where signaling molecules (neurotransmitters) are released by the presynaptic neuron, and they influence electrical activity of another neuron (postsynaptic neuron). The inherent probabilistic release of neurotransmitters is a significant source of noise that critically impacts the timing of spikes (action potential) in the postsynaptic neuron. We develop a stochastic model that incorporates noise mechanisms in synaptic transmission, such as, random docking of neurotransmitter-filled vesicle to a finite number of docking sites, with each site having a probability of vesicle release upon arrival of an action potential. This random, burst-like release of neurotransmitters serves as an input to an integrate-and-fire model, where spikes in the postsynaptic neuron are triggered when its membrane potential reaches a critical threshold for the first time. We derive novel analytical results for the probability distribution function of spike timing, and systematically investigate how underlying model parameters and noise processes regulate variability in the inter-spike times. Interestingly, in some parameter regimes, independent arrivals of action potentials in the presynaptic neuron generate strong dependencies in the spike timing of the postsynaptic neuron. Finally, we argue that probabilistic release of neurotransmitters is not only a source of disturbance, but plays a beneficial role in synaptic information processing.

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

2002 ◽  
Vol 283 (3) ◽  
pp. H1031-H1041 ◽  
Author(s):  
Gui-Rong Li ◽  
Chu-Pak Lau ◽  
Anique Ducharme ◽  
Jean-Claude Tardif ◽  
Stanley Nattel
Keyword(s):  
Left Ventricle ◽  
Action Potential ◽  
Action Potentials ◽  
Slow Component ◽  
Ionic Current ◽  
Ionic Currents ◽  
Cell Types ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Early Afterdepolarizations

Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K+ current ( I K1) was homogeneously reduced by ∼41% (at −60 mV) in the three cell types. Transient outward K+ current ( I to1) was decreased by 43–45% at +30 mV, and the slow component of the delayed rectifier K+ current ( I Ks) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K+ current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of I K1, I to1, and I Ks increases APD and favors occurrence of EADs.

L-364,373 (R-L3) enantiomers have opposite modulating effects on IKs in mammalian ventricular myocytes

2013 ◽  
Vol 91 (8) ◽  
pp. 586-592 ◽  
Author(s):  
Claudia Corici ◽  
Zsófia Kohajda ◽  
Attila Kristóf ◽  
András Horváth ◽  
László Virág ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Guinea Pig ◽  
Action Potential ◽  
Right Ventricular ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Ventricular Arrhythmias ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Whole Cell Patch Clamp

Activators of the slow delayed rectifier K+ current (IKs) have been suggested as promising tools for suppressing ventricular arrhythmias due to prolongation of repolarization. Recently, L-364,373 (R-L3) was nominated to activate IKs in myocytes from several species; however, in some studies, it failed to activate IKs. One later study suggested opposite modulating effects from the R-L3 enantiomers as a possible explanation for this discrepancy. Therefore, we analyzed the effect of the RL-3 enantiomers on IKs in ventricular mammalian myocytes, by applying standard microelectrode and whole-cell patch-clamp techniques at 37 °C. We synthesized 2 substances, ZS_1270B (right) and ZS_1271B (left), the 2 enantiomers of R-L3. In rabbit myocytes, ZS_1270B enhanced the IKs tail current by approximately 30%, whereas ZS_1271B reduced IKs tails by 45%. In guinea pig right ventricular preparations, ZS_1270B shortened APD90 (action potential duration measured at 90% repolarization) by 12%, whereas ZS_1271B lengthened it by approximately 15%. We concluded that R-L3 enantiomers in the same concentration range indeed have opposite modulating effects on IKs, which may explain why the racemic drug R-L3 previously failed to activate IKs. ZS_1270B is a potent IKs activator, therefore, this substance is appropriate to test whether IKs activators are ideal tools to suppress ventricular arrhythmias originating from prolongation of action potentials.

Ionic currents during action potentials in mammalian skeletal muscle fibers analyzed with loose patch clamp

1994 ◽  
Vol 267 (6) ◽  
pp. C1699-C1706 ◽  
Author(s):  
H. Wolters ◽  
W. Wallinga ◽  
D. L. Ypey ◽  
H. B. Boom
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Action Potentials ◽  
Potassium Current ◽  
Sodium Current ◽  
Delayed Rectifier ◽  
Mammalian Skeletal Muscle ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Patch Clamp Technique

The loose patch-clamp technique was applied to analyze transmembrane currents during propagating action potentials in superficial fibers of musculi extensor digitorum longus of the mouse in vitro. Experimentally three components were identified in the transmembrane current: 1) a capacitive, 2) an inward sodium, and 3) an outward potassium current. Other components were negligible. The capacitive current was similar in shape to the first derivative of the intracellularly measured action potential. Tetrodotoxin, tetraethylammonium, and 4-aminopyridine, applied in the pipette, were used to identify the contribution in the current by sodium and potassium ions. With extracellularly applied depolarization steps only a sodium current was observed, not a potassium current. Occasionally found outward currents were artifactual. The behaviour of delayed rectifier potassium channels in muscle fiber membranes is discussed in the light of these unexpected findings. We conclude that potassium channel activity contributing to and measured during action potential generation is in some way inaccessible to loose patch extracellular voltage-clamp stimulation and that loose patch action current recording is a useful noninvasive method to analyze membrane conductances involved in action potential generation.

scholarly journals Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 754 ◽  
Author(s):  
Dumitru A. Iacobas ◽  
Sanda Iacobas ◽  
Philip R. Lee ◽  
Jonathan E. Cohen ◽  
R. Douglas Fields
Keyword(s):  
Transcription Factors ◽  
Action Potential ◽  
Calcium Signaling ◽  
Action Potentials ◽  
Pearson Correlation ◽  
Temporal Coding ◽  
Transcriptional Networks ◽  
Action Potential Firing ◽  
Transcriptional Responses ◽  
Potential Firing

Transcriptional responses to the appropriate temporal pattern of action potential firing are essential for long-term adaption of neuronal properties to the functional activity of neural circuits and environmental experience. However, standard transcriptome analysis methods can be too limited in identifying critical aspects that coordinate temporal coding of action potential firing with transcriptome response. A Pearson correlation analysis was applied to determine how pairs of genes in the mouse dorsal root ganglion (DRG) neurons are coordinately expressed in response to stimulation producing the same number of action potentials by two different temporal patterns. Analysis of 4728 distinct gene-pairs related to calcium signaling, 435,711 pairs of transcription factors, 820 pairs of voltage-gated ion channels, and 86,862 pairs of calcium signaling genes with transcription factors indicated that genes become coordinately activated by distinct action potential firing patterns and this depends on the duration of stimulation. Moreover, a measure of expression variance revealed that the control of transcripts abundances is sensitive to the pattern of stimulation. Thus, action potentials impact intracellular signaling and the transcriptome in dynamic manner that not only alter gene expression levels significantly (as previously reported) but also affects the control of their expression fluctuations and profoundly remodel the transcriptional networks.

scholarly journals Etomidate Reduces Initiation of Backpropagating Dendritic Action Potentials: Implications for Sensory Processing and Synaptic Plasticity During Anesthesia

2007 ◽  
Vol 97 (3) ◽  
pp. 2373-2384 ◽  
Author(s):  
Erwin H. van den Burg ◽  
Jacob Engelmann ◽  
João Bacelo ◽  
Leonel Gómez ◽  
Kirsty Grant
Keyword(s):  
Action Potential ◽  
Sensory Processing ◽  
Action Potentials ◽  
Molecular Layer ◽  
Current Source ◽  
Spike Timing ◽  
Stimulus Strength ◽  
Action Potential Initiation ◽  
Potential Initiation

Anesthetics may induce specific changes that alter the balance of activity within neural networks. Here we describe the effects of the GABAA receptor potentiating anesthetic etomidate on sensory processing, studied in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in vitro. Previous studies have shown that the ELL integrates sensory input and removes predictable features by comparing reafferent sensory signals with a descending electromotor command-driven corollary signal that arrives in part through parallel fiber synapses with the apical dendrites of GABAergic interneurons. These synapses show spike timing–dependent depression when presynaptic activation is associated with postsynaptic backpropagating dendritic action potentials. Under etomidate, almost all neurons become tonically hyperpolarized. The threshold for action potential initiation increased for both synaptic activation and direct intracellular depolarization. Synaptically evoked inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and prolonged. Current source density analysis showed that backpropagation of action potentials through the apical dendritic arborization in the molecular layer was reduced but could be restored by increasing stimulus strength. These effects of etomidate were blocked by bicuculline or picrotoxin. It is concluded that etomidate affects both tonic and phasic inhibitory conductances at GABAA receptors and that increased shunting inhibition at the level of the proximal dendrites also contributes to increasing the threshold for action potential backpropagation. When stimulus strength is sufficient to evoke backpropagation, repetitive association of synaptic excitation with postsynaptic action potential initiation still results in synaptic depression, showing that etomidate does not interfere with the molecular mechanism underlying plastic modulation.

scholarly journals Effects of Ropivacaine on Action Potential Configuration and Ion Currents in Isolated Canine Ventricular Cardiomyocytes

2008 ◽  
Vol 108 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Adrienn Szabó ◽  
Norbert Szentandrássy ◽  
Péter Birinyi ◽  
Balázs Horváth ◽  
Gergely Szabó ◽  
...  
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Action Potentials ◽  
Potassium Current ◽  
Maximum Velocity ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Ventricular Cardiomyocytes ◽  
Delayed Rectifier Potassium Current ◽  
Action Potential Configuration

Background Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes. Methods Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents. Results Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm). Conclusions Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.

scholarly journals A bidirectional associative memory based on cortical spiking neurons using temporal coding

2021 ◽  
Author(s):  
Masood Zamani
Keyword(s):  
Neural Networks ◽  
Associative Memory ◽  
Action Potentials ◽  
Storage Capacity ◽  
Spike Timing ◽  
Temporal Coding ◽  
Spiking Neurons ◽  
Biological Plausibility ◽  
Bidirectional Associative Memory ◽  
Coding Scheme

In this thesis, we proposed a spiking bidirectional associative memory (BAM) using temporal coding. The information processing in biological neurons is beyond of[sic] that applied in the current Artificial Neural Networks (ANNs). The coding scheme used in ANNs known as “mean firing rate” cannot answer the fast and complex computations occurring in the cortex. In biological neural networks the information is coded and processed based on the timing of action potentials. To improve the biological plausibility of the standard BAM, we employed spiking neurons for its processing units, and information is presented to the BAM in the form of temporal coding. The neurons employed in the model are heterogeneous, and being able to generate various spike-timing patterns. Genetic Algorithm and Co-evolution are used for training, and the experiment results of the proposed BAM are compared to those of the standard BAM. The results show improvements in recall, storage capacity and convergence which are of interest to design a BAM.

Separation of neuron types in the gustatory zone of the nucleus tractus solitarii on the basis of intrinsic firing properties

1992 ◽  
Vol 67 (6) ◽  
pp. 1659-1668 ◽  
Author(s):  
R. M. Bradley ◽  
R. D. Sweazey
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Input Resistance ◽  
Group Iv ◽  
Nucleus Tractus Solitarii ◽  
Discharge Pattern ◽  
Membrane Hyperpolarization ◽  
Group Iii ◽  
Group I ◽  
Group Ii

1. Whole-cell current-clamp recordings were made from neurons in the rostral nucleus tractus solitarii (NTS) in an in vitro brain slice preparation in rats. On the basis of previous investigations, these neurons are believed to be involved with processing of gustatory as well as somatosensory information. 2. Rostral NTS neurons had a mean resting membrane potential of -47 mV. The mean input resistance was 336 M omega, and by fitting a double exponential function the membrane time constant had fast (2.3 ms) and slow (20.6 ms) components. 3. Neurons were separated into four different groups on the basis of their responses to a current injection pulse paradigm consisting of membrane hyperpolarization of different magnitudes and durations immediately followed by a long (1.200 ms) depolarizing pulse. The regular repetitive discharge pattern of the first group of neurons (Group I neurons) was changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons either delayed the occurrence of the first action potential or increased the length of the first interspike interval in the action-potential train produced by membrane depolarization. The length of the delay was related both to the magnitude and duration of the hyperpolarizing prepulse. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of action potentials that was often shortened by prior hyperpolarization of the neuron. 4. Differences exist in other intrinsic properties of the four neuron groups. Group I and III neurons were capable of initiating the highest frequency of action potentials to a 100-pA 1,200-ms depolarizing pulse. In response to a short depolarizing pulse. Group II neurons had the longest latency to the first spike and responded with the fewest action potentials. Group IV neurons tended to have higher input resistance and membrane time constants than the other neuron groups. A subset of neurons in each neuron group showed membrane afterhyperpolarizations (AHP) after depolarization-induced action-potential trains (postburst AHP). Postburst AHP amplitudes ranged from 1.0 to 12.9 mV and were of greatest magnitude in Group II neurons. Postburst AHP durations ranged from 75 to 3,538 ms and were of longest duration in neurons belonging to Group III. Group II neurons, which had the largest postburst AHP magnitude, had the shortest postburst AHP duration. 5. These results demonstrate that neurons in the rostral NTS can be separated on the basis of their intrinsic membrane properties.(ABSTRACT TRUNCATED AT 400 WORDS)

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