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.

Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Resting Potential ◽  
Model Parameters ◽  
Voltage Sensitivity ◽  
Whole Cell ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

Dynamics of sensory afferent synaptic transmission in aortic baroreceptor regions on nucleus tractus solitarius

1995 ◽  
Vol 74 (4) ◽  
pp. 1518-1528 ◽  
Author(s):  
M. C. Andresen ◽  
M. Yang
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Frequency Response ◽  
Action Potentials ◽  
Nucleus Tractus Solitarius ◽  
Reversal Potential ◽  
Constant Frequency ◽  
Epsp Amplitude ◽  
Postsynaptic Potentials ◽  
Medial Nucleus

1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to solitary tract (ST) activation were studied in a horizontal brain slice preparation of the rat medulla. Slices included sections of ST sufficiently long that the ST could be electrically activated several millimeters from the recording site of cell bodies in mNTS. 2. Three types of synaptic events were evoked in response to ST stimulation: simple excitatory postsynaptic potentials (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/- 0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP amplitude increased linearly with increasing hyperpolarization, with an extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With 1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5. With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally comparable average EPSPs were evoked during constant and burst patterns of ST stimulation. The amplitude of the initial EPSP in each burst was very well maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited action potentials and suppressed spontaneous spiking, but higher frequencies led to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic stimulation-suppression cycle clearly entrained action potential activity to the ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action potentials with each pulse to higher frequencies (50 Hz) without failures, and entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as 50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST stimulation frequency-response relation of these IPSPs was similar to that for the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear to be activated polysynaptically via a glutamatergic-GABAergic sequence in response to ST activation. 9. The results suggest that sensory afferent synapses in mNTS have limited transmission of high-frequency inputs. Both synaptic transmission and the characteristics of the postsynaptic neuron importantly contribute to the action potential transmission from afferent to NTS neuron and beyond. This overall frequency response limitation may contribute to the accommodation of reflex responses from sensory afferent inputs such as arterial baroreceptors within their physiological discharge frequency range.

Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart

2015 ◽  
Vol 93 (9) ◽  
pp. 803-810 ◽  
Author(s):  
Norbert Nagy ◽  
Tamás Szél ◽  
Norbert Jost ◽  
András Tóth ◽  
Julius Gy. Papp ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Human Heart ◽  
Expression Profiles ◽  
Purkinje Fibre ◽  
Purkinje Fibres ◽  
Repolarization Reserve ◽  
Protein Expression Profiles ◽  
First Time

Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K+ currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

scholarly journals Action Potential Propagation and Synchronisation in Myelinated Axons

2019 ◽  
Author(s):  
Helmut Schmidt ◽  
Thomas R. Knösche
Keyword(s):  
White Matter ◽  
Action Potential ◽  
Myelin Sheath ◽  
Action Potentials ◽  
Structural Parameters ◽  
Node Of Ranvier ◽  
Model Parameters ◽  
Mathematical Framework ◽  
Whole Brain ◽  
Action Potential Propagation

AbstractWith the advent of advanced MRI techniques it has become possible to study axonal white matter non-invasively and in great detail. Measuring the various parameters of the long-range connections of the brain opens up the possibility to build and refine detailed models of large-scale neuronal activity. One particular challenge is to find a mathematical description of action potential propagation that is sufficiently simple, yet still biologically plausible to model signal transmission across entire axonal fibre bundles. We develop a mathematical framework in which we replace the Hodgkin-Huxley dynamics by a spike-diffuse-spike model with passive sub-threshold dynamics and explicit, threshold-activated ion channel currents. This allows us to study in detail the influence of the various model parameters on the action potential velocity and on the entrainment of action potentials between ephaptically coupled fibres without having to recur to numerical simulations. Specifically, we recover known results regarding the influence of axon diameter, node of Ranvier length and internode length on the velocity of action potentials. Additionally, we find that the velocity depends more strongly on the thickness of the myelin sheath than was suggested by previous theoretical studies. We further explain the slowing down and synchronisation of action potentials in ephaptically coupled fibres by their dynamic interaction. In summary, this study presents a solution to incorporate detailed axonal parameters into a whole-brain modelling framework.Author summaryWith more and more data becoming available on white-matter tracts, the need arises to develop modelling frameworks that incorporate these data at the whole-brain level. This requires the development of efficient mathematical schemes to study parameter dependencies that can then be matched with data, in particular the speed of action potentials that cause delays between brain regions. Here, we develop a method that describes the formation of action potentials by threshold activated currents, often referred to as spike-diffuse-spike modelling. A particular focus of our study is the dependence of the speed of action potentials on structural parameters. We find that the diameter of axons and the thickness of the myelin sheath have a strong influence on the speed, whereas the length of myelinated segments and node of Ranvier length have a lesser effect. In addition to examining single axons, we demonstrate that action potentials between nearby axons can synchronise and slow down their propagation speed.

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.

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.

scholarly journals Suppression of sensory to motor synaptic transmission and narrowing of the sensory neurone action potential by arginine vasotocin in Aplysia californica

1987 ◽  
Vol 128 (1) ◽  
pp. 47-62
Author(s):  
J. Goldberg ◽  
W. Colmers ◽  
J. Edstrom ◽  
K. Lukowiak
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potentials ◽  
Physiological Role ◽  
Arginine Vasotocin ◽  
Sensory Cells ◽  
Sensory Neurone ◽  
Single Action ◽  
Withdrawal Reflex ◽  
Homosynaptic Depression

The vertebrate neurohypophysial peptide arginine vasotocin (AVT), which may be endogenous to the Aplysia central nervous system, was tested for its effect on sensory to motor neurone synaptic transmission. In the semi-intact preparation, superfusion of AVT (10(−6) moll-1) over the abdominal ganglion decreased the amplitude of both the gill withdrawal reflex and the short-latency excitatory postsynaptic potentials (EPSPs) evoked in gill and siphon motor neurones by single action potentials elicited in sensory neurones. AVT slowed the rate of rise of the EPSP, enhanced the rate of homosynaptic depression, and reversibly decreased the duration of the action potential of mechanosensory neurones in isolated, perfused abdominal and pleural ganglia. Frequency-dependent prolongation of action potentials of pleural sensory cells was also decreased by application of AVT. Because this peptide has been shown to modulate the gill withdrawal reflex and its subsequent habituation, the hypothesis that AVT plays a physiological role in the expression of the suppressed behavioural state is proposed. In addition, it is proposed that modulation of the reflex by AVT occurs in part by shortening the duration of the sensory neurone action potential.

Transmembranal Action Potentials From Pregnant Uterus

1956 ◽  
Vol 187 (2) ◽  
pp. 338-340 ◽  
Author(s):  
J. Walter Woodbury ◽  
Donald M. McIntyre
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Guinea Pigs ◽  
Action Potentials ◽  
Resting Potential ◽  
Pregnant Uterus ◽  
Uterine Muscle ◽  
Order Of Magnitude ◽  
The Mean ◽  
First Time

For the first time overshooting action potentials of pregnant guinea pig uterus have been recorded intracellularly. Flexibly mounted ultramicroelectrodes were used. The largest action potential (AP) seen was 48 mv with an associated resting potential (RP) of 38 mv. The mean of 129 measurements of RP in four guinea pigs was 32.6 mv. The mean of 86 AP's was 21.9 mv. Although overshoot was seen only occasionally, the action potentials were always of the same order of magnitude as the resting potentials. It seems probable that the excitable mechanisms of uterine muscle though labile and variable are closely similar to those of other tissues.

scholarly journals Social-ecological analysis of timely rice planting in Eastern India

2021 ◽  
Vol 41 (2) ◽  
Author(s):  
Anton Urfels ◽  
Andrew J. McDonald ◽  
Gerardo van Halsema ◽  
Paul C. Struik ◽  
Pankaj Kumar ◽  
...  
Keyword(s):  
Agricultural Development ◽  
Wildlife Conservation ◽  
Geographic Region ◽  
Critical Threshold ◽  
Enabling Factors ◽  
Gangetic Plains ◽  
Land Type ◽  
Groundwater Availability ◽  
Agricultural Input ◽  
First Time

AbstractTimely crop planting is a foundation for climate-resilient rice-wheat systems of the Eastern Gangetic Plains—a global food insecurity and poverty hotspot. We hypothesize that the capacity of individual farmers to plant on time varies considerably, shaped by multifaceted enabling factors and constraints that are poorly understood. To address this knowledge gap, two complementary datasets were used to characterize drivers and decision processes that govern the timing of rice planting in this region. The first dataset was a large agricultural management survey (rice-wheat: n = 15,245; of which rice: n = 7597) from a broad geographic region that was analyzed by machine learning methods. The second dataset was a discussion-based survey (n = 112) from a more limited geography that we analyzed with graph theory tools to elicit nuanced information on planting decisions. By combining insights from these methods, we show for the first time that differences in rice planting times are primarily shaped by ecosystem and climate factors while social factors play a prominent secondary role. Monsoon onset, surface and groundwater availability, and land type determine village-scale mean planting times whereas, for resource-constrained farmers who tend to plant later ceteris paribus, planting is further influenced by access to farm machinery, seed, fertilizer, and labor. Also, a critical threshold for economically efficient pumping appears at a groundwater depth of around 4.5 m; below this depth, farmers do not irrigate and delay planting. Without collective action to spread risk through synchronous timely planting, ecosystem factors such as threats posed by pests and wild animals may further deter early planting by individual farmers. Accordingly, we propose a three-pronged strategy that combines targeted strengthening of agricultural input chains, agroadvisory development, and coordinated rice planting and wildlife conservation to support climate-resilient agricultural development in the Eastern Gangetic Plains.

scholarly journals Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1516
Author(s):  
Daniel Gratz ◽  
Alexander J Winkle ◽  
Seth H Weinberg ◽  
Thomas J Hund
Keyword(s):  
Action Potential ◽  
Mathematical Models ◽  
Cardiac Myocyte ◽  
Population Level ◽  
Na Channel ◽  
Model Parameters ◽  
Healthy Population ◽  
Experimental Measurements ◽  
Voltage Gated ◽  
Experimental Variability

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.

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