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1.
Phys Rev Lett ; 127(9): 098101, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506203

RESUMO

Cardiac fibrosis is a well-known arrhythmogenic condition which can lead to sudden cardiac death. Physically, fibrosis can be viewed as a large number of small obstacles in an excitable medium, which may create nonlinear wave turbulence or reentry. The relation between the specific texture of fibrosis and the onset of reentry is of great theoretical and practical importance. Here, we present a conceptual framework which combines functional aspects of propagation manifested as conduction blocks, with reentry wavelength and geometrical clusters of fibrosis. We formulate them into the single concept of minimal functional cluster and through extensive simulations show that it characterizes the path of reexcitation accurately, and importantly its size distribution quantitatively predicts the reentry probability for different fibrosis densities and tissue excitabilities.


Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Modelos Cardiovasculares , Miocárdio/patologia , Potenciais de Ação , Análise por Conglomerados , Fibrose/patologia , Fibrose/fisiopatologia , Humanos , Dinâmica não Linear
2.
Comput Intell Neurosci ; 2021: 3285719, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484319

RESUMO

The nonlinear spiking neural P systems (NSNP systems) are new types of computation models, in which the state of neurons is represented by real numbers, and nonlinear spiking rules handle the neuron's firing. In this work, in order to improve computing performance, the weights and delays are introduced to the NSNP system, and universal nonlinear spiking neural P systems with delays and weights on synapses (NSNP-DW) are proposed. Weights are treated as multiplicative constants by which the number of spikes is increased when transiting across synapses, and delays take into account the speed at which the synapses between neurons transmit information. As a distributed parallel computing model, the Turing universality of the NSNP-DW system as number generating and accepting devices is proven. 47 and 43 neurons are sufficient for constructing two small universal NSNP-DW systems. The NSNP-DW system solving the Subset Sum problem is also presented in this work.


Assuntos
Modelos Neurológicos , Redes Neurais de Computação , Potenciais de Ação , Neurônios , Sinapses
3.
Neuron ; 109(17): 2707-2716.e6, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473954

RESUMO

The strychnine-sensitive pentameric glycine receptor (GlyR) mediates fast inhibitory neurotransmission in the mammalian nervous system. Only heteromeric GlyRs mediate synaptic transmission, as they contain the ß subunit that permits clustering at the synapse through its interaction with scaffolding proteins. Here, we show that α2 and ß subunits assemble with an unexpected 4:1 stoichiometry to produce GlyR with native electrophysiological properties. We determined structures in multiple functional states at 3.6-3.8 Å resolutions and show how 4:1 stoichiometry is consistent with the structural features of α2ß GlyR. Furthermore, we show that one single ß subunit in each GlyR gives rise to the characteristic electrophysiological properties of heteromeric GlyR, while more ß subunits render GlyR non-conductive. A single ß subunit ensures a univalent GlyR-scaffold linkage, which means the scaffold alone regulates the cluster properties.


Assuntos
Simulação de Dinâmica Molecular , Multimerização Proteica , Receptores de Glicina/química , Potenciais de Ação , Animais , Células HEK293 , Humanos , Bicamadas Lipídicas/metabolismo , Subunidades Proteicas , Receptores de Glicina/metabolismo , Células Sf9 , Spodoptera
4.
Chaos ; 31(8): 083112, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34470229

RESUMO

We develop a circular cumulant representation for the recurrent network of quadratic integrate-and-fire neurons subject to noise. The synaptic coupling is global or macroscopically equivalent to it. We assume a Lorentzian distribution of the parameter controlling whether the isolated individual neuron is periodically spiking or excitable. For the infinite chain of circular cumulant equations, a hierarchy of smallness is identified; on the basis of it, we truncate the chain and suggest several two-cumulant neural mass models. These models allow one to go beyond the Ott-Antonsen Ansatz and describe the effect of noise on hysteretic transitions between macroscopic regimes of a population with inhibitory coupling. The accuracy of two-cumulant models is analyzed in detail.


Assuntos
Modelos Neurológicos , Rede Nervosa , Potenciais de Ação , Neurônios , Ruído
5.
Chaos ; 31(8): 083128, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34470231

RESUMO

Oscillatory activities in the brain, detected by electroencephalograms, have identified synchronization patterns. These synchronized activities in neurons are related to cognitive processes. Additionally, experimental research studies on neuronal rhythms have shown synchronous oscillations in brain disorders. Mathematical modeling of networks has been used to mimic these neuronal synchronizations. Actually, networks with scale-free properties were identified in some regions of the cortex. In this work, to investigate these brain synchronizations, we focus on neuronal synchronization in a network with coupled scale-free networks. The networks are connected according to a topological organization in the structural cortical regions of the human brain. The neuronal dynamic is given by the Rulkov model, which is a two-dimensional iterated map. The Rulkov neuron can generate quiescence, tonic spiking, and bursting. Depending on the parameters, we identify synchronous behavior among the neurons in the clustered networks. In this work, we aim to suppress the neuronal burst synchronization by the application of an external perturbation as a function of the mean-field of membrane potential. We found that the method we used to suppress synchronization presents better results when compared to the time-delayed feedback method when applied to the same model of the neuronal network.


Assuntos
Modelos Neurológicos , Rede Nervosa , Potenciais de Ação , Retroalimentação , Humanos , Neurônios
6.
Adv Physiol Educ ; 45(4): 702-708, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34498935

RESUMO

Patch-clamp electrophysiological recordings of neuronal activity require a large amount of space and equipment. The technique is difficult to master and not conducive to demonstration to more than a few medical students. Therefore, neurophysiological education is mostly limited to classroom-based pedagogies such as lectures. However, the demonstration of concepts such as changes in membrane potential and ion channel activity is best achieved with hands-on approaches. This article details an in silico activity suitable for large groups of medical students that demonstrates the key concepts in neurophysiology using the LabAXON simulation software. Learning activities in our practical include 1) measurements of voltage and time parameters of the neuronal action potential and its relationship to the Nernst potentials of Na+ and K+; 2) determination of the stimulus threshold to evoke action potentials; 3) demonstration of the refractory period of an action potential; and 4) voltage-clamp experiments to determine the current-voltage relationship of voltage-gated Na+ and K+ channels and the voltage dependence of, and recovery from, inactivation of voltage-gated Na+ channels. We emphasized the accuracy of quantitative measurements as well as the correct use of units. The level of difficulty of the activity can be altered through different multiple choice questions relating to material introduced in the associated lectures. This practical activity is suitable for different class sizes and is adaptable for delivery with online platforms. Student feedback showed that the students felt the activity helped them consolidate their understanding of the lecture material.


Assuntos
Neurofisiologia , Estudantes de Medicina , Potenciais de Ação , Humanos , Potenciais da Membrana , Sódio
7.
Nat Commun ; 12(1): 5245, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475396

RESUMO

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.


Assuntos
Eletrodos Implantados , Eletrofisiologia/métodos , Espaço Extracelular/fisiologia , Silício/química , Potenciais de Ação , Animais , Encéfalo/fisiologia , Eletrofisiologia/instrumentação , Desenho de Equipamento , Camundongos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Processamento de Sinais Assistido por Computador
8.
Comput Intell Neurosci ; 2021: 9954302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539774

RESUMO

Neurophysiological studies have shown that there is a close relationship between spikes and local field potential (LFP), which reflects crucial neural coding information. In this paper, we used a new method to evaluate the synchronization between spikes and LFP. All possible phases of LFP from -π to π were first binned into a freely chosen number of bins; then, the probability of spikes falling in each bin was calculated, and the deviation degree from the uniform distribution based on the Kullback-Leibler divergence was calculated to define the synchronization between spikes and LFP. The simulation results demonstrate that the method is rapid, basically unaffected by the total number of spikes, and can adequately resist the noise of spike trains. We applied this method to the experimental data of patients with intractable epilepsy, and we observed the synchronization between spikes and LFP in the formation of memory. These results show that our proposed method is a powerful tool that can quantitatively measure the synchronization between spikes and LFP.


Assuntos
Neurônios , Neurofisiologia , Potenciais de Ação , Simulação por Computador , Humanos
9.
Nat Commun ; 12(1): 4816, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376652

RESUMO

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. We tested this idea using high-resolution, pattern-based fMRI analyses. Here we show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. The magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide insight into why remapping occurs.


Assuntos
Potenciais de Ação/fisiologia , Região CA3 Hipocampal/fisiologia , Giro Denteado/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Região CA3 Hipocampal/diagnóstico por imagem , Giro Denteado/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa/métodos , Adulto Jovem
10.
Nat Commun ; 12(1): 4830, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376663

RESUMO

Choice-relevant brain regions in prefrontal cortex may progressively transform information about options into choices. Here, we examine responses of neurons in four regions of the medial prefrontal cortex as macaques performed two-option risky choices. All four regions encode economic variables in similar proportions and show similar putative signatures of key choice-related computations. We provide evidence to support a gradient of function that proceeds from areas 14 to 25 to 32 to 24. Specifically, we show that decodability of twelve distinct task variables increases along that path, consistent with the idea that regions that are higher in the anatomical hierarchy make choice-relevant variables more separable. We also show progressively longer intrinsic timescales in the same series. Together these results highlight the importance of the medial wall in choice, endorse a specific gradient-based organization, and argue against a modular functional neuroanatomy of choice.


Assuntos
Comportamento de Escolha/fisiologia , Macaca mulatta/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodos , Modelos Neurológicos , Córtex Pré-Frontal/citologia
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 445-448, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374268

RESUMO

Objective: To introduce a method of marking neurons using patch clamp technique. Methods: The brain slices of the target area was cut with a vibrating microtome. The glass microelectrode was perfused with the electrode liquid containing NeurobiotinTM Tracer, and the whole-cell patch-clamp recording was performed. After recording, the brain slices were fixed and rinsed with 4% paraformaldehyde. After stained in phosphate buffer with Streptavidin-Texas Red and Triton X-100 for at least 2 hours, the neurons can be observed under a fluorescence microscope. Results: The cell membrane voltage was clamped at -70 mV, and the neuron showed a gradually increasing membrane current after step stimulation. When recording in the current clamp mode, the step stimulus caused the neuron to depolarize to the threshold potential and then burst into action potentials. The morphology of intact neurons with clear cell body and protrusions of a neuron could be observed under a fluorescence microscope. Conclusion: This method is suitable for observing the morphological features of the recorded neuron after patch clamp experiments, which is easy to operate, and the image is intuitive and clear.


Assuntos
Encéfalo , Neurônios , Potenciais de Ação , Técnicas de Patch-Clamp
12.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437090

RESUMO

The ability to perceive and respond to environmental stimuli emerges in the absence of sensory experience. Spontaneous retinal activity prior to eye opening guides the refinement of retinotopy and eye-specific segregation in mammals, but its role in the development of higher-order visual response properties remains unclear. Here, we describe a transient window in neonatal mouse development during which the spatial propagation of spontaneous retinal waves resembles the optic flow pattern generated by forward self-motion. We show that wave directionality requires the same circuit components that form the adult direction-selective retinal circuit and that chronic disruption of wave directionality alters the development of direction-selective responses of superior colliculus neurons. These data demonstrate how the developing visual system patterns spontaneous activity to simulate ethologically relevant features of the external world and thereby instruct self-organization.


Assuntos
Fluxo Óptico , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia , Vias Visuais , Potenciais de Ação , Células Amácrinas/fisiologia , Animais , Animais Recém-Nascidos , Axônios/fisiologia , Proteínas do Citoesqueleto/genética , Camundongos , Movimento (Física) , Mutação , Piridazinas/farmacologia , Receptores de GABA-A/metabolismo , Retina/crescimento & desenvolvimento , Análise Espaço-Temporal , Colículos Superiores/fisiologia
13.
Anesth Analg ; 133(3): 781-793, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34403389

RESUMO

BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.


Assuntos
Período de Recuperação da Anestesia , Anestesia por Inalação , Anestésicos Inalatórios/farmacologia , Estado de Consciência/efeitos dos fármacos , Desflurano/farmacologia , Isoflurano/farmacologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Orexinas/farmacologia , Potenciais de Ação , Animais , Eletroencefalografia , Masculino , Núcleos da Linha Média do Tálamo/metabolismo , Neurônios/metabolismo , Optogenética , Receptores de Orexina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
14.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361012

RESUMO

Loss-of-function mutations in the KV4.3 channel-encoding KCND3 gene are linked to neurodegenerative cerebellar ataxia. Patients suffering from neurodegeneration associated with iron deposition may also present with cerebellar ataxia. The mechanism underlying brain iron accumulation remains unclear. Here, we aim to ascertain the potential pathogenic role of KCND3 variant in iron accumulation-related cerebellar ataxia. We presented a patient with slowly progressive cerebellar ataxia, parkinsonism, cognitive impairment, and iron accumulation in the basal ganglia and the cerebellum. Whole exome sequencing analyses identified in the patient a heterozygous KCND3 c.1256G>A (p.R419H) variant predicted to be disease-causing by multiple bioinformatic analyses. In vitro biochemical and immunofluorescence examinations revealed that, compared to the human KV4.3 wild-type channel, the p.R419H variant exhibited normal protein abundance and subcellular localization pattern. Electrophysiological investigation, however, demonstrated that the KV4.3 p.R419H variant was associated with a dominant increase in potassium current amplitudes, as well as notable changes in voltage-dependent gating properties leading to enhanced potassium window current. These observations indicate that, in direct contrast with the loss-of-function KCND3 mutations previously reported in cerebellar ataxia patients, we identified a rare gain-of-function KCND3 variant that may expand the clinical and molecular spectra of neurodegenerative cerebellar disorders associated with brain iron accumulation.


Assuntos
Disfunção Cognitiva/genética , Mutação com Ganho de Função , Ferro/metabolismo , Transtornos Parkinsonianos/genética , Canais de Potássio Shal/genética , Ataxias Espinocerebelares/genética , Potenciais de Ação , Idoso , Encéfalo/metabolismo , Disfunção Cognitiva/patologia , Células HEK293 , Humanos , Masculino , Transtornos Parkinsonianos/patologia , Domínios Proteicos , Canais de Potássio Shal/química , Canais de Potássio Shal/metabolismo , Ataxias Espinocerebelares/patologia
15.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34380658

RESUMO

GABAergic somatodendritic inhibition in the preBötzinger complex (preBötC), a medullary site for the generation of inspiratory rhythm, is involved in respiratory rhythmogenesis and patterning. Nevertheless, whether GABA acts distally on presynaptic terminals, evoking presynaptic inhibition is unknown. Here, we begin to address this problem by measuring presynaptic Ca2+ transients in preBötC neurons, under rhythmic and non-rhythmic conditions, with two variants of genetically encoded Ca2+ indicators (GECIs). Organotypic slice cultures from newborn mice, containing the preBötC, were drop-transduced with jGCaMP7s, or injected with jGCaMP7f-labeling commissural preBötC neurons. Then, Ca2+ imaging combined with whole-cell patch-clamp or field stimulation was obtained from inspiratory preBötC neurons. We found that rhythmically active neurons expressed synchronized Ca2+ transients in soma, proximal and distal dendritic regions, and punctate synapse-like structures. Expansion microscopy revealed morphologic characteristics of bona fide synaptic boutons of the en passant and terminal type. Under non-rhythmic conditions, we found that bath application of the GABAA receptor agonist muscimol, and local microiontophoresis of GABA, reduced action potential (AP)-evoked and field stimulus-evoked Ca2+ transients in presynaptic terminals in inspiratory neurons and commissural neurons projecting to the contralateral preBötC. In addition, under rhythmic conditions, network rhythmic activity was suppressed by muscimol, while the GABAA receptor antagonist bicuculline completely re-activated spontaneous activity. These observations demonstrate that the preBötC includes neurons that show GABAergic inhibition of presynaptic Ca2+ transients, and presynaptic inhibition may play a role in the network activity that underlies breathing.


Assuntos
Bulbo , Neurônios , Potenciais de Ação , Animais , Camundongos , Respiração , Sinapses
16.
Nat Neurosci ; 24(9): 1324-1337, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34341584

RESUMO

Inference of action potentials ('spikes') from neuronal calcium signals is complicated by the scarcity of simultaneous measurements of action potentials and calcium signals ('ground truth'). In this study, we compiled a large, diverse ground truth database from publicly available and newly performed recordings in zebrafish and mice covering a broad range of calcium indicators, cell types and signal-to-noise ratios, comprising a total of more than 35 recording hours from 298 neurons. We developed an algorithm for spike inference (termed CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates and outperforms existing model-based algorithms. To optimize performance for unseen imaging data, CASCADE retrains itself by resampling ground truth data to match the respective sampling rate and noise level; therefore, no parameters need to be adjusted by the user. In addition, we developed systematic performance assessments for unseen data, openly released a resource toolbox and provide a user-friendly cloud-based implementation.


Assuntos
Artefatos , Encéfalo/fisiologia , Aprendizado Profundo , Neuroimagem/métodos , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Animais , Cálcio/metabolismo , Bases de Dados Factuais , Camundongos , Modelos Neurológicos , Peixe-Zebra
17.
Science ; 373(6552): 343-348, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34437154

RESUMO

Spatial memory in vertebrates requires brain regions homologous to the mammalian hippocampus. Between vertebrate clades, however, these regions are anatomically distinct and appear to produce different spatial patterns of neural activity. We asked whether hippocampal activity is fundamentally different even between distant vertebrates that share a strong dependence on spatial memory. We studied tufted titmice, food-caching birds capable of remembering many concealed food locations. We found mammalian-like neural activity in the titmouse hippocampus, including sharp-wave ripples and anatomically organized place cells. In a non-food-caching bird species, spatial firing was less informative and was exhibited by fewer neurons. These findings suggest that hippocampal circuit mechanisms are similar between birds and mammals, but that the resulting patterns of activity may vary quantitatively with species-specific ethological needs.


Assuntos
Tentilhões/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Passeriformes/fisiologia , Células de Lugar/fisiologia , Memória Espacial , Potenciais de Ação , Animais , Fenômenos Eletrofisiológicos , Comportamento Alimentar , Feminino , Tentilhões/anatomia & histologia , Hipocampo/anatomia & histologia , Hipocampo/citologia , Masculino , Vias Neurais , Passeriformes/anatomia & histologia , Sono
18.
Chaos ; 31(7): 073137, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340346

RESUMO

Arrhythmogenic early afterdepolarizations (EADs) are investigated in a biophysically detailed mathematical model of a rabbit ventricular myocyte, providing their location in the parameter phase space and describing their dynamical mechanisms. Simulations using the Sato model, defined by 27 state variables and 177 parameters, are conducted to generate electrical action potentials (APs) for different values of the pacing cycle length and other parameters related to sodium and calcium concentrations. A detailed study of the different AP patterns with or without EADs is carried out, showing the presence of a high variety of temporal AP configurations with chaotic and quasiperiodic behaviors. Regions of bistability are identified and, importantly, linked to transitions between different behaviors. Using sweeping techniques, one-, two-, and three-parameter phase spaces are provided, allowing ascertainment of the role of the selected parameters as well as location of the transition regions. A Devil's staircase, with symbolic sequence analysis, is proposed to describe transitions in the ratio between the number of voltage (EAD and AP) peaks and the number of APs. To conclude, the obtained results are linked to recent studies for low-dimensional models and a conjecture is made for the internal dynamical structure of the transition region from non-EAD to EAD behavior using fold and cusp bifurcations and maximal canards.


Assuntos
Modelos Cardiovasculares , Miócitos Cardíacos , Potenciais de Ação , Animais , Arritmias Cardíacas , Cálcio , Coelhos
19.
Chaos ; 31(7): 073144, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340360

RESUMO

In this paper, we study the propagation of the cardiac action potential in a one-dimensional fiber, where cells are electrically coupled through gap junctions (GJs). We consider gap junctional gate dynamics that depend on the intercellular potential. We find that different GJs in the tissue can end up in two different states: a low conducting state and a high conducting state. We first present evidence of the dynamical multistability that occurs by setting specific parameters of the GJ dynamics. Subsequently, we explain how the multistability is a direct consequence of the GJ stability problem by reducing the dynamical system's dimensions. The conductance dispersion usually occurs on a large time scale, i.e., thousands of heartbeats. The full cardiac model simulations are computationally demanding, and we derive a simplified model that allows for a reduction in the computational cost of four orders of magnitude. This simplified model reproduces nearly quantitatively the results provided by the original full model. We explain the discrepancies between the two models due to the simplified model's lack of spatial correlations. This simplified model provides a valuable tool to explore cardiac dynamics over very long time scales. That is highly relevant in studying diseases that develop on a large time scale compared to the basic heartbeat. As in the brain, plasticity and tissue remodeling are crucial parameters in determining the action potential wave propagation's stability.


Assuntos
Junções Comunicantes , Coração , Potenciais de Ação
20.
Chaos ; 31(7): 073123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340362

RESUMO

Cardiac electrophysiology modeling deals with a complex network of excitable cells forming an intricate syncytium: the heart. The electrical activity of the heart shows recurrent spatial patterns of activation, known as cardiac alternans, featuring multiscale emerging behavior. On these grounds, we propose a novel mathematical formulation for cardiac electrophysiology modeling and simulation incorporating spatially non-local couplings within a physiological reaction-diffusion scenario. In particular, we formulate, a space-fractional electrophysiological framework, extending and generalizing similar works conducted for the monodomain model. We characterize one-dimensional excitation patterns by performing an extended numerical analysis encompassing a broad spectrum of space-fractional derivative powers and various intra- and extracellular conductivity combinations. Our numerical study demonstrates that (i) symmetric properties occur in the conductivity parameters' space following the proposed theoretical framework, (ii) the degree of non-local coupling affects the onset and evolution of discordant alternans dynamics, and (iii) the theoretical framework fully recovers classical formulations and is amenable for parametric tuning relying on experimental conduction velocity and action potential morphology.


Assuntos
Técnicas Eletrofisiológicas Cardíacas , Modelos Cardiovasculares , Potenciais de Ação , Simulação por Computador , Coração
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