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1.
Neuroscience Bulletin ; (6): 1-13, 2023.
Article in English | WPRIM | ID: wpr-971533

ABSTRACT

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.


Subject(s)
Axon Initial Segment , Axons/physiology , Neurons , Synapses/physiology , Pyramidal Cells/physiology , Interneurons/physiology , Action Potentials/physiology
2.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 200-205, 2023.
Article in Chinese | WPRIM | ID: wpr-971434

ABSTRACT

Objective: To investigate the application of cochlear nerve action potential (CNAP) monitoring in the resection of vestibular schwannoma, especially evaluating its significance for hearing preservation. Methods: From April 2018 to December 2021, 54 patients with vestibular schwannoma who underwent resection via retrosigmoid approach were collected in Chinese PLA General Hospital. Before surgery, all patients had effective hearing (AAO-HNS grade C or above). Brainstem auditory evoked potential (BAEP) combined with CNAP monitoring was performed during surgery. The CNAP monitoring was combined with continuous monitoring and cochlear nerve mapping. And patients were divided into hearing preservation group and non-preserved group according to postoperative AAO-HNS grade. SPSS 23.0 software was used to analyze the differences of CNAP and BEAP parameters between the two groups. Results: A total of 54 patients completed intraoperative monitoring and data collection, including 25 males (46.3%) and 29 females (53.7%), aged 27-71 years with an average age of 46.2 years. The maximum tumor diameter were (18.1±5.9) mm (range 10-34 mm). All tumors were totally removed with preserved facial nerve function (House-Brackmann grade I-II). The hearing preservation rate of 54 patients was 51.9% (28/54). During surgery, the V wave extraction rate of BAEP waveform was 85.2% (46/54) before tumor resection, 71.4% (20/28) in the hearing preservation group after tumor resection, and disappeared in the hearing preservation group (0/26). CNAP waveform was elicited in 54 patients during operation. Differences were found in the distribution of CNAP waveforms after tumor resection. The waveforms of the hearing-preserving group were triphasic and biphasic, while those in the non-preserving group were low-level and positive. For hearing preservation group, the amplitude of N1 wave after tumor resection was significantly higher than that before tumor resection[14.45(7.54, 33.85)μV vs 9.13(4.88, 23.35)μV, P=0.022]; However, for the non-preserved group, the amplitude of N1 wave after tumor resection was significantly lower than that before tumor resection [3.07(1.96, 4.60)μV vs 6.55(4.54, 9.71)μV, P=0.007]; After tumor resection, the amplitude was significantly higher than that of the unreserved group [14.45(7.54, 33.85)μV vs 3.07(1.96, 4.60)μV, P<0.001]. Conclusions: BAEP combined with CNAP monitoring is conducive to intraoperative hearing protection, and the application of cochlear nerve mapping can prompt the surgeon to avoid nerve injury. The waveform and N1 amplitude of CNAP after tumor resection have a certain value in predicting postoperative hearing preservation status.


Subject(s)
Female , Male , Humans , Middle Aged , Neuroma, Acoustic/surgery , Action Potentials , Evoked Potentials, Auditory, Brain Stem , Cochlea , Cochlear Nerve
3.
Journal of Biomedical Engineering ; (6): 859-866, 2023.
Article in Chinese | WPRIM | ID: wpr-1008910

ABSTRACT

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.


Subject(s)
Action Potentials/physiology , Computer Simulation , Models, Neurological , Stochastic Processes , Neurons/physiology , Electromagnetic Phenomena
4.
Journal of Biomedical Engineering ; (6): 692-699, 2023.
Article in Chinese | WPRIM | ID: wpr-1008889

ABSTRACT

With inherent sparse spike-based coding and asynchronous event-driven computation, spiking neural network (SNN) is naturally suitable for processing event stream data of event cameras. In order to improve the feature extraction and classification performance of bio-inspired hierarchical SNNs, in this paper an event camera object recognition system based on biological synaptic plasticity is proposed. In our system input event streams were firstly segmented adaptively using spiking neuron potential to improve computational efficiency of the system. Multi-layer feature learning and classification are implemented by our bio-inspired hierarchical SNN with synaptic plasticity. After Gabor filter-based event-driven convolution layer which extracted primary visual features of event streams, we used a feature learning layer with unsupervised spiking timing dependent plasticity (STDP) rule to help the network extract frequent salient features, and a feature learning layer with reward-modulated STDP rule to help the network learn diagnostic features. The classification accuracies of the network proposed in this paper on the four benchmark event stream datasets were better than the existing bio-inspired hierarchical SNNs. Moreover, our method showed good classification ability for short event stream input data, and was robust to input event stream noise. The results show that our method can improve the feature extraction and classification performance of this kind of SNNs for event camera object recognition.


Subject(s)
Visual Perception , Learning , Action Potentials , Neural Networks, Computer , Neuronal Plasticity
5.
Acta Physiologica Sinica ; (6): 359-369, 2022.
Article in Chinese | WPRIM | ID: wpr-939571

ABSTRACT

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABAA receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.


Subject(s)
Animals , Mice , Action Potentials/physiology , Cerebellar Cortex/metabolism , Cerebellum/metabolism , Norepinephrine/pharmacology , Purkinje Cells/metabolism , Receptors, Adrenergic, alpha-2/metabolism , Receptors, GABA-A/metabolism
6.
Neuroscience Bulletin ; (6): 135-148, 2022.
Article in English | WPRIM | ID: wpr-922667

ABSTRACT

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.


Subject(s)
Humans , Action Potentials , HEK293 Cells , Protein Kinase C/metabolism , Pyramidal Cells/enzymology , Shab Potassium Channels/genetics
7.
Chinese Journal of Applied Physiology ; (6): 85-90, 2022.
Article in Chinese | WPRIM | ID: wpr-927903

ABSTRACT

Objective: To compare the difference between the built-in and external reference electrode of microwire electrode array in the process of recording rat brain neuron firings, optimizing the production and embedding of the microwire electrode array, and providing a more affordable and excellent media tool for multi-channel electrophysiological real-time recording system. Methods: A 16 channel microwire electrode array was made by using nickel chromium alloy wires, circuit board, electrode pin and ground wires (silver wires). The reference electrode of the microwire electrode array was built-in (the reference electrode and electrode array were arranged in parallel) or external (the reference electrode and ground wire were welded at both ends of one side of the electrode), and the difference between the two electrodes was observed and compared in recording neuronal discharges in ACC brain area of rats. Experimental rats were divided into built-in group and external group, n=8-9. The test indicators included signal-to-noise ratio (n=8), discharge amplitude (n=380) and discharge frequency (n=54). Results: The microwire electrode array with both built-in and external reference electrodes successfully recorded the electrical signals of neurons in the ACC brain region of rats. Compared with the external group, the electrical signals of neurons in built-in group had the advantages of a higher signal-to-noise ratio (P<0.05), a smaller amplitude of background signals and less noise interference, and a larger discharge amplitude(P<0.05); there was no significant difference in spike discharge frequency recorded by these two types of electrodes (P>0.05). Conclusion: When recording the electrical activity of neurons in the ACC brain region of rats, the microwire electrode array with built-in reference electrode recorded electrical signals with higher signal-to-noise ratio and larger discharge amplitude, providing a more reliable tool for multi-channel electrophysiology technology.


Subject(s)
Animals , Rats , Action Potentials/physiology , Brain , Electrophysiological Phenomena , Microelectrodes , Neurons
8.
Neuroscience Bulletin ; (6): 505-518, 2022.
Article in English | WPRIM | ID: wpr-929088

ABSTRACT

The axon initial segment (AIS) is a specialized structure that controls neuronal excitability via action potential (AP) generation. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI (chicken ovalbumin upstream promotor-transcription factor 1) is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation. Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation, they strengthen and weaken, respectively, the receiving spontaneous network in mutant neurons. In contrast, overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation, but decreases the receiving spontaneous network. Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.


Subject(s)
Animals , Mice , Action Potentials , Axon Initial Segment , COUP Transcription Factor I , DNA-Binding Proteins/physiology , Mammals , Transcription Factors
9.
Journal of Biomedical Engineering ; (6): 1081-1086, 2021.
Article in Chinese | WPRIM | ID: wpr-921848

ABSTRACT

In this paper, a new surface electromyography (sEMG) signal decomposition method based on spatial location is proposed for the high-density sEMG signals in dynamic muscle contraction. Firstly, according to the waveform correlation of each muscle motor units (MU) in each channel, the firing times are extracted, and then the firing times are classified by the spatial location of MU. The MU firing trains are finally obtained. The simulation results show that the accuracy rate of a single MU firing train after classification is more than 91.67%. For real sEMG signals, the accuracy rate to find a same MU by the "two source" method is over (88.3 ± 2.1)%. This paper provides a new idea for dynamic sEMG signal decomposition.


Subject(s)
Action Potentials , Computer Simulation , Electromyography , Muscle Contraction , Muscle, Skeletal
10.
Journal of Biomedical Engineering ; (6): 232-240, 2021.
Article in Chinese | WPRIM | ID: wpr-879270

ABSTRACT

Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.


Subject(s)
Action Potentials , Computer Simulation , Electric Stimulation , Evoked Potentials , Spinal Cord , Spinal Cord Stimulation
11.
Journal of Biomedical Engineering ; (6): 224-231, 2021.
Article in Chinese | WPRIM | ID: wpr-879269

ABSTRACT

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) is widely used in the clinical treatment of neurological and psychiatric diseases, but the mechanism of its action is still unclear. The purpose of this paper is to investigate the effects of different frequencies of magnetic stimulation (MS) on neuronal excitability and voltage-gated potassium channels in the


Subject(s)
Animals , Mice , Action Potentials , Magnetic Phenomena , Mental Disorders , Neurons , Patch-Clamp Techniques , Potassium Channels, Voltage-Gated
12.
Braz. arch. biol. technol ; 64: e21200245, 2021. tab, graf
Article in English | LILACS | ID: biblio-1278434

ABSTRACT

Abstract Current trends in science education recommend the complementary use of virtual and hands-on methods of teaching. In neurobiology, for instance, there is a plethora of virtual laboratories and simulators that can be readily combined with traditional physical labs. Unfortunately, physical laboratories are almost unaffordable for many institutions due to the high cost of equipment. In this paper, we present a simple and low-cost in vivo method for demonstrating some of the basic biophysical properties of neural action potentials. The method involves the following steps: a) dissection of the ventral nerve cord of earthworm; b) electrical stimulation; c) amplification and visualization of the medial and lateral giant fibers' action potentials; and d) recording. The system showed stability, expected amplification, high signal-to-noise ratio, and an estimated total cost of US$ 5.662. We provide guidelines for assembling the system and discus its utility as a teaching alternative for low budget institutions.


Subject(s)
Neurobiology/methods , Action Potentials , Low Cost Technology/economics , Schools
14.
Arq. bras. cardiol ; 114(4): 732-735, Abr. 2020. graf
Article in English, Portuguese | LILACS, SES-SP | ID: biblio-1131189

ABSTRACT

Resumo A Ranolazina (RANO), conhecida na clínica como Ranexa, é um fármaco que previne a arritmia cardíaca através da inibição da corrente de sódio tardia (INaT). Um gradiente de voltagem transmural do canal Nav1.5 encontra-se na parede ventricular esquerda do coração. Assim, investigamos os efeitos da RANO em cardiomiócitos saudáveis e em modelo celular da Síndrome do QT longo tipo 3 (SQTL tipo 3). Usamos células isoladas do endocárdio (ENDO) e do epicárdio (EPI) e um software de medição com detecção de bordas por vídeo e microscopia de fluorescência para monitorar os transientes de cálcio. A RANO (0,1, 1, 10 e 30 uM, a 25OC) em uma série de frequências de estimulação teve impacto pouco significativo sobre ambos os tipos de células, mas a RANO (30uM) a 35OC minimizou o encurtamento dos sarcômeros em ~21% para células do endocárdio. Em seguida, para simular a SQTL tipo 3, as células do ENDO e EPI foram expostas à toxina ATX-II da anêmona do mar, que aumenta a INaT. As arritmias celulares induzidas por ATX-II foram suprimidas com o uso da RANO (30 µM) a 35OC. Com base nesses resultados, podemos concluir que a RANO tem um impacto pouco significativo sobre o encurtamento dos sarcômeros de células saudáveis do ENDO e EPI. Além disso, ela suprime as arritmias induzidas por INaT para níveis semelhantes nas células do ENDO e EPI.


Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.


Subject(s)
Humans , Arrhythmias, Cardiac/drug therapy , Long QT Syndrome , Ranolazine/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Action Potentials , Cardiac Conduction System Disease
15.
Journal of Biomedical Engineering ; (6): 863-874, 2020.
Article in Chinese | WPRIM | ID: wpr-879214

ABSTRACT

The method of directly using speed information and angle information to drive attractors model of grid cells to encode environment has poor anti-interference ability and is not bionic. In response to the problem, this paper proposes a grid field calculation model based on perceived speed and perceived angle. The model has the following characteristics. Firstly, visual stream is decoded to obtain visual speed, and speed cell is modeled and decoded to obtain body speed. Visual speed and body speed are integrated to obtain perceived speed information. Secondly, a one-dimensional circularly connected cell model with excitatory connection is used to simulate the firing mechanism of head direction cells, so that the robot obtains current perception angle information in a biomimetic manner. Finally, the two kinds of perceptual information of speed and angle are combined to realize the driving of grid cell attractors model. The proposed model was experimentally verified. The results showed that this model could realize periodic hexagonal firing field mode of grid cells and precise path integration function. The proposed algorithm may provide a foundation for the research on construction method of robot cognitive map based on hippocampal cognition mechanism.


Subject(s)
Action Potentials , Computer Simulation , Computer Systems , Entorhinal Cortex , Grid Cells , Hippocampus , Models, Neurological
16.
Acta Physiologica Sinica ; (6): 757-764, 2020.
Article in English | WPRIM | ID: wpr-878223

ABSTRACT

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.


Subject(s)
Animals , Mice , Action Potentials , Calcium/metabolism , Myocytes, Cardiac/metabolism , Sodium/metabolism , Sodium-Calcium Exchanger , Thiourea/pharmacology
17.
Arq. neuropsiquiatr ; 77(8): 550-554, Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019466

ABSTRACT

ABSTRACT Quantitative electromyography is an important tool to evaluate myopathies, and some difficult-to-treat asthmatic patients may have a subclinical corticosteroid myopathic process, using only inhaled corticosteroid, according to some studies. In this report, diaphragm quantitative electromyography was used to evaluate asthmatic difficult-to-treat patients, comparing them with a control group. Significant differences were obtained in amplitude, duration and size index of motor unit action potentials, with lower parameters in the asthmatic patients, which may indicate a myopathic process.


RESUMO Eletromiografia quantitativa é uma ferramenta importante para a avaliação de miopatias, e alguns pacientes asmáticos de difícil controle podem ter um processo miopático subclínico, mesmo usando apenas corticosteroides inalatórios, de acordo com alguns artigos. Nesse artigo a eletromiografia quantitativa do diafragma foi usada para avaliar os pacientes asmáticos de difícil controle, comparando com um grupo controle. Diferenças significativas nas amplitudes, durações e índices de tamanho dos potenciais de unidades motoras foram encontradas, com parâmetros mais baixos nos pacientes asmáticos, o que pode indicar um processo miopático.


Subject(s)
Humans , Male , Female , Adult , Aged , Young Adult , Asthma/physiopathology , Diaphragm/physiopathology , Electromyography/methods , Reference Values , Asthma/drug therapy , Time Factors , Action Potentials/physiology , Case-Control Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Statistics, Nonparametric
18.
Translational and Clinical Pharmacology ; : 12-18, 2019.
Article in English | WPRIM | ID: wpr-742427

ABSTRACT

In 2005, the International Council for Harmonization (ICH) established cardiotoxicity assessment guidelines to identify the risk of Torsade de Pointes (TdP). It is focused on the blockade of the human ether-à-go-go-related gene (hERG) channel known to cause QT/QTc prolongation and the QT/QTc prolongation shown on the electrocardiogram. However, these biomarkers are not the direct risks of TdP with low specificity as the action potential is influenced by multiple channels along with the hERG channel. Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative emerged to address limitations of the current model. The objective of CiPA is to develop a standardized in silico model of a human ventricular cell to quantitively evaluate the cardiac response for the cardiac toxicity risk and to come up with a metric for the TdP risk assessment. In silico working group under CiPA developed a standardized and reliable in silico model and a metric that can quantitatively evaluate cellular cardiac electrophysiologic activity. The implementation mainly consists of hERG fitting, Hill fitting, and action potential simulation. In this review, we explained how the in silico model of CiPA works, and briefly summarized current overall CiPA studies. We hope this review helps clinical pharmacologists to understand the underlying estimation process of CiPA in silico modeling.


Subject(s)
Humans , Action Potentials , Biomarkers , Cardiotoxicity , Computer Simulation , Electrocardiography , Hope , In Vitro Techniques , Risk Assessment , Sensitivity and Specificity , Torsades de Pointes
19.
Journal of Biomedical Engineering ; (6): 902-910, 2019.
Article in Chinese | WPRIM | ID: wpr-781848

ABSTRACT

Biological neural networks have dual properties of small-world attributes and scale-free attributes. Most of the current researches on neural networks are based on small-world networks or scale-free networks with lower clustering coefficient, however, the real brain network is a scale-free network with small-world attributes. In this paper, a scale-free spiking neural network with high clustering coefficient and small-world attribute was constructed. The dynamic evolution process was analyzed from three aspects: synaptic regulation process, firing characteristics and complex network characteristics. The experimental results show that, as time goes by, the synaptic strength gradually decreases and tends to be stable. As a result, the connection strength of the network decreases and tends to be stable; the firing rate of neurons gradually decreases and tends to be stable, and the synchronization becomes worse; the local information transmission efficiency is stable, the global information transmission efficiency is reduced and tends to be stable, and the small-world attributes are relatively stable. The dynamic characteristics vary with time and interact with each other. The regulation of synapses is based on the firing time of neurons, and the regulation of synapses will affect the firing of neurons and complex characteristics of networks. In this paper, a scale-free spiking neural network was constructed, which has biological authenticity. It lays a foundation for the research of artificial neural network and its engineering application.


Subject(s)
Action Potentials , Models, Neurological , Neural Networks, Computer , Neuronal Plasticity , Synapses
20.
Chinese Journal of Applied Physiology ; (6): 232-238, 2019.
Article in Chinese | WPRIM | ID: wpr-776523

ABSTRACT

OBJECTIVE@#To quantitatively investigate the effects of Ringer's solution with different concentrations of alcohol (1%~80%) on biphasic compound action potentials (AP) from frog sciatic nerve trunk, and their recoveries from alcohol effects.@*METHODS@#Individual segments of frog sciatic nerve trunk with a length of 6 to 8 cm were prepared. Ringer's solution with different concentrations of alcohol (0%, 1%, 2%, 4%, 8%, 16%, 32%, 48%, 64% and 80%) was applied onto the segment of the trunk between the stimulus and ground electrodes via an agent reservoir which was newly armed in a nerve trunk shielded chamber for 5 minutes. The nerve trunk was respectively electro-stimulated to generate the biphasic compound AP which was recorded using the experimental system of BL-420F. This was followed by 5 times washout plus 5 min administration with Ringer's solution before recovery recording of AP.@*RESULTS@#Compared to normal Ringer's solution, Ringer's solution with alcohol at ≤4% did not have dramatic impacts on the AP amplitude and conduction velocity, while Ringer's solution with alcohol at ≥8% there was significant decrease in these two parameters. Ringer's solution with alcohol at the conentrations of 16%, 32% and ≥48% could prevent a small proportion (30%), a large proportion (90%) and all (100%) of sciatic nerve trunks, respectively, from generating AP. Washout with normal Ringer's solution after alcohol application at the concentration of ≤32%, AP could totally recover to normal status. While alcohol at the concentration of 48%, 64% and 80%, the probabilities to regenerate APs were 90%, 40% and 0%, and the AP amplitudes were decreased to 60%, 36% and 0%, respectively. After washout, AP conduction velocity showed no difference with alcohol at the concentration of ≤8% when compared with that before washout, while it could not be recovered to normal under alcohol at ≥16%.@*CONCLUSION@#Ringer's solution with different concentrations of alcohol exerts different effects on biphasic compound AP amplitude and conduction velocity. Hopefully, our findings could be helpful for the alcoholic usage and its recovery from alcoholic damage.


Subject(s)
Animals , Action Potentials , Anura , Ethanol , Pharmacology , Ringer's Solution , Pharmacology , Sciatic Nerve
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