Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve domi...Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.展开更多
Neurologists define the transmission of nerve impulses across the membranes of the neural cells as a result of difference in the concentration of ions while they measured an electric potential, called as an action pot...Neurologists define the transmission of nerve impulses across the membranes of the neural cells as a result of difference in the concentration of ions while they measured an electric potential, called as an action potential, which allows the propagation of such nerve impulses as electrical signals. Such measurements should guide them to a logical explanation of the nerve impulses as electric charges driven by the measured action potential. However, such logical conclusion, or explanation, is ignored due to a wrong definition of the flow of electric charges as a flow of electrons that cannot pass through neural networks. According to recent studies, electric charges are properly defined as electromagnetic (EM) waves whose energy is expressed as the product of its propagating electric potential times their entropy flow which is adhered to the flow of such energy. Such definition matches the logical conclusion of the nerve impulses as electric charges, as previously explained, and defines the entropy of the neural network, measured by Ammeters, in Watt or Joule/Volt. The measured entropy represents a neurodiagnostic property of the neural networks that measures its capacity to allow the flow of energy per unit action potential. Theoretical verification of the innovative definition of nerve impulses is presented by following an advanced entropy approach. A proper review of the machine records of the stimulating electric charges, used in the diagnosis of the neural networks, and the stimulated nerve impulses or stimulated responses, represents practical verifications of the innovative definitions of the electric charges and the nerve impulses. Comparing the functioning of the thermoelectric generators and the brain neurons, such neurons are defined as thermoelectric generators of the electric nerve impulses and their propagating, or action, potential.展开更多
In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the ...In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the paper is that, for the case of biophysically inhomogeneous axon tracts, the compound action potential is governed by a Hodgkin-Huxley like equation itself in certain cases. The paper extends an earlier result for the identical axon case.展开更多
ECAPs are the summary of multiple neurons' spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtrac...ECAPs are the summary of multiple neurons' spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm.Three kinds of FDA approved cochlear implants support ECAP testing.This article is to summarize the clinical application of ECAP lest.ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery.In recent years.ECAP thresholds are also used to estimate the T levels and C levels helping programming.However,correlation between ECAP thresholds and psychophysical thresholds is affected by many factors.So far,ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.展开更多
Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kineti...Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.展开更多
This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 c...This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 chronic stroke subjects.Various parameters were derived from the CMAP scan to examine paretic muscle changes,including CMAP amplitude,D50,step index(STEPIX)and amplitude index(AMPIX).A significant decrease in CMAP amplitude and STEPIX was observed in paretic muscles compared with contralateral muscles(CMAP amplitude:paretic(9.0±0.5)mV,contralateral(11.3±0.9)mV,P=0.024;STEPIX:paretic 101.2±7.6,contralateral 121.9±6.5,P=0.020).No significant difference in D50 and AMPIX was observed between the paretic and contralateral sides(P>0.05).The findings revealed complex paretic muscle changes including motor unit degeneration,muscle fiber denervation,reinnervation and atrophy,providing useful insights to help understand neuromuscular mechanisms associated with weakness and other functional deterioration post stroke.The CMAP scan experimental protocols and the applied processing methods are noninvasive,convenient,and automated,offering practical benefits for clinical application.展开更多
The back-propagating action potential(bpAP)is crucial for neuronal signal integration and synaptic plasticity in dendritic trees.Its properties(velocity and amplitude)can be affected by dendritic morphology.Due to lim...The back-propagating action potential(bpAP)is crucial for neuronal signal integration and synaptic plasticity in dendritic trees.Its properties(velocity and amplitude)can be affected by dendritic morphology.Due to limited spatial resolution,it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology,such as the dendrite diameter and branching pattern,using patch-clamp recording.By taking advantage of Optopatch,an all-optical electrophysiological method,we made detailed recordings of the real-time propagation of bpAPs in dendritic trees.We found that the velocity of bpAPs was not uniform in a single dendrite,and the bpAP velocity differed among distinct dendrites of the same neuron.The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated.In addition,when bpAPs passed through a dendritic branch point,their velocity decreased significantly.Similar to velocity,the amplitude of bpAPs was also positively correlated with dendritic diameter,and the attenuation patterns of bpAPs differed among different dendrites.Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results.These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs.The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology.These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology,to further illuminate the role of bpAPs in neuronal communication.展开更多
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 neur...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.展开更多
Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson’s disease. Micro electrochemical carbon
Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induc...Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.展开更多
This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between ...This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between conduction velocity and the impulse profile. Computer simulations are used to bolster the analysis.展开更多
Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative,anxiolytic,and analgesic effects.Dexketoprofen,which is used as an analgesic,is a nonselective nonsteroidal anti-inflammator...Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative,anxiolytic,and analgesic effects.Dexketoprofen,which is used as an analgesic,is a nonselective nonsteroidal anti-inflammatory drug (NSAID).The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing.In this study,we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve.The isolated sciatic nerve from adult rats was transferred to a nerve chamber.The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods.Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10–9 to 10–5 M,and the CAPs were recorded for 5 and 10 minutes.The CAP parameters were calculated.Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group,i.e.,the group in which rats did not receive treatment.CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen.Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers;however,dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner.These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action.The experimental procedures were approved by the Necmettin Erbakan University on January 30,2013 (approval No.2013-024).展开更多
Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and ...Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.展开更多
Repolarization heterogeneity(RH)is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram(ECG).Exceeding the physiologically based RH level is associated with appearan...Repolarization heterogeneity(RH)is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram(ECG).Exceeding the physiologically based RH level is associated with appearance of life-threatening ventricular arrhythmias and sudden cardiac death.In this regard,an accurate and comprehensive evaluation of the degree of RH parameters is of importance for assessment of heart state and arrhythmic risk.This review is devoted to comprehensive consideration of RH phenomena in terms of electrophysiological processes underlying RH,cardiac electric field formation during ventricular repolarization,as well as clinical significance of RH and its reflection on ECG parameters.The formation of transmural,apicobasal,left-toright and anterior-posterior gradients of action potential durations and end of repolarization times resulting from the heterogenous distribution of repolarizing ion currents and action potential morphology throughout the heart ventricles,and the different sensitivity of myocardial cells in different ventricular regions to the action of pharmacological agents,temperature,frequency of stimulation,etc.,are being discussed.The review is focused on the fact that RH has different aspects–temporal and spatial,global and local;ECG reflection of various RH aspects and their clinical significance are being discussed.Strategies for comprehensive assessment of ventricular RH using different ECG indices reflecting various RH aspects are presented.展开更多
Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple br...Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple branches of an extratemporal segment.However,in the clinical treatment of facial nerve defects,allogeneic donors are limited.In this experiment,we exposed the left trunk and multiple branches of the extratemporal segment in six rhesus monkeys and dissected a gap of 25 mm to construct a monkey model of a whole left nerve defect.Six monkeys were randomly assigned to an autograft group or a xenogeneic acellular nerve graft group.In the autograft group,the 25-mm whole facial nerve defect was immediately bridged using an autogenous ipsilateral great auricular nerve,and in the xenogeneic acellular nerve graft group,this was done using a xenogeneic acellular nerve graft with trunk-branches.Examinations of facial symmetry,nerve-muscle electrophysiology,retrograde transport of labeled neuronal tracers,and morphology of the regenerated nerve and target muscle at 8 months postoperatively showed that the faces of the monkey appeared to be symmetrical in the static state and slightly asymmetrical during facial movement,and that they could actively close their eyelids completely.The degree of recovery from facial paralysis reached House-Brackmann grade II in both groups.Compound muscle action potentials were recorded and orbicularis oris muscles responded to electro-stimuli on the surgical side in each monkey.Fluoro Gold-labeled neurons could be detected in the facial nuclei on the injured side.Immunohistochemical staining showed abundant neurofilament-200-positive axons and soluble protein-100-positive Schwann cells in the regenerated nerves.A large number of mid-graft myelinated axons were observed via methylene blue staining and a transmission electron microscope.Taken together,our data indicate that xenogeneic acellular nerve grafts from minipigs are safe and effective for repairing whole facial nerve defects in rhesus monkeys,with an effect similar to that of autologous nerve transplantation.Thus,a xenogeneic acellular nerve graft may be a suitable choice for bridging a whole facial nerve defect if no other method is available.The study was approved by the Laboratory Animal Management Committee and the Ethics Review Committee of the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University,China(approval No.2018-D-1)on March 15,2018.展开更多
BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation are the main causes for sudden cardiac death. This study aime...BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits.METHODS: Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups: sham-operated(SHAM) group(n=8), MI group(n=8) and MI with ramipril(RAM) group(n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confi rmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril(1 mg/kg per day) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fi brillation(VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student's t test and ANOVA were used for statistical analysis.RESULTS: VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks(2.6±0.8 vs. 12.4±2.9, P<0.05). Twelve weeks after MI, the duration of repolarization for 90%(APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI(258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7, P<0.05). However, the APD90 was not signif icantly different at 12 weeks before and after MI in the RAM group(P>0.05). Moreover, the transmural dispersion of repolarization(TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups(36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P<0.05). But the TDR was not signifi cantly different between the RAM and SHAM groups(18.7±6.2 vs. 24.9±8.7, P>0.05).CONCLUSION: Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.展开更多
As hybrid cochlear implant devices are increasingly used for restoring hearing in patients with residual hearing, it is important to understand electrically evoked responses in cochleae having functional hair cells. T...As hybrid cochlear implant devices are increasingly used for restoring hearing in patients with residual hearing, it is important to understand electrically evoked responses in cochleae having functional hair cells. To test the hypothesis that extracochlear electrical stimulation (EES) from sinusoidal current can provoke an auditory nerve response with normal frequency selectivity, the EES-evoked compound action potential(ECAP) was investigated in this study. Brief sinusoidal electrical currents, delivered via a round window electrode, were used to evoke ECAP. The ECAP waveform was observed to be the same as the acoustically evoked CAP(ACAP), except for a shorter latency. The input/output and intensity/latency functions of ACAPs and ECAPs were also similar. The maximum acoustic masking for both ACAP and ECAP occurred near probe frequencies. Since the masked tuning curve of a CAP reflects the frequency selectivity of neural excitation, these data demonstrate a highly specific activation of the auditory nerve, which would result in high degree of frequency selectivity. This frequency selectivity likely results from the cochlear traveling wave caused by electrically stimulated outer hair cells.展开更多
BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and...BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81873784,82071426Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DSF)。
文摘Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.
文摘Neurologists define the transmission of nerve impulses across the membranes of the neural cells as a result of difference in the concentration of ions while they measured an electric potential, called as an action potential, which allows the propagation of such nerve impulses as electrical signals. Such measurements should guide them to a logical explanation of the nerve impulses as electric charges driven by the measured action potential. However, such logical conclusion, or explanation, is ignored due to a wrong definition of the flow of electric charges as a flow of electrons that cannot pass through neural networks. According to recent studies, electric charges are properly defined as electromagnetic (EM) waves whose energy is expressed as the product of its propagating electric potential times their entropy flow which is adhered to the flow of such energy. Such definition matches the logical conclusion of the nerve impulses as electric charges, as previously explained, and defines the entropy of the neural network, measured by Ammeters, in Watt or Joule/Volt. The measured entropy represents a neurodiagnostic property of the neural networks that measures its capacity to allow the flow of energy per unit action potential. Theoretical verification of the innovative definition of nerve impulses is presented by following an advanced entropy approach. A proper review of the machine records of the stimulating electric charges, used in the diagnosis of the neural networks, and the stimulated nerve impulses or stimulated responses, represents practical verifications of the innovative definitions of the electric charges and the nerve impulses. Comparing the functioning of the thermoelectric generators and the brain neurons, such neurons are defined as thermoelectric generators of the electric nerve impulses and their propagating, or action, potential.
文摘In this paper, the authors investigate compound action potentials formed when the underlying tract's axons have current-mediated coupling amongst themselves, and no field-mediated coupling. The key finding of the paper is that, for the case of biophysically inhomogeneous axon tracts, the compound action potential is governed by a Hodgkin-Huxley like equation itself in certain cases. The paper extends an earlier result for the identical axon case.
基金supported by grants from the National Basic Research Program of China(973 Program)(#2012CB967900)Science and Technology Innovation Nursery Foundation of PLA General Hospital(13KMM14)Clinical Research Supporting Foundation of PLA General Hospital(2012FC-TSYS-3056)
文摘ECAPs are the summary of multiple neurons' spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm.Three kinds of FDA approved cochlear implants support ECAP testing.This article is to summarize the clinical application of ECAP lest.ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery.In recent years.ECAP thresholds are also used to estimate the T levels and C levels helping programming.However,correlation between ECAP thresholds and psychophysical thresholds is affected by many factors.So far,ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.
基金supported by the National Science and Technology Innovation 2030-Major Program of “Brain Science and Brain-Like Research”(2022ZD0211800)National Natural Science Foundation of China General Research Grant (81971679, 21727806,31771147)+4 种基金Major Research Grant (91632305, 32088101)Ministry of Science and Technology (2018YFA0507600, 2017YFA0503600)Qidong-PKU SLS Innovation Fund (2016000663)Fundamental Research Funds for the Central Universities and National Key R&D Program of China (2020AAA0105200)sponsored by the Bayer Investigator Award。
文摘Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.
基金supported by the National Natural Science Foundation of China(82102179)the Shandong Provincial Natural Science Foundation(ZR2020KF012,ZR2021QH267,ZR2021QH053)+2 种基金the Shanghai Municipal Key Clinical Specialty(shslczdzk02701)the National Institutes of Health(7 R21 NS113716-02)the National Institute on Disability and Rehabilitation Research(90REMM0001-01-00).
文摘This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 chronic stroke subjects.Various parameters were derived from the CMAP scan to examine paretic muscle changes,including CMAP amplitude,D50,step index(STEPIX)and amplitude index(AMPIX).A significant decrease in CMAP amplitude and STEPIX was observed in paretic muscles compared with contralateral muscles(CMAP amplitude:paretic(9.0±0.5)mV,contralateral(11.3±0.9)mV,P=0.024;STEPIX:paretic 101.2±7.6,contralateral 121.9±6.5,P=0.020).No significant difference in D50 and AMPIX was observed between the paretic and contralateral sides(P>0.05).The findings revealed complex paretic muscle changes including motor unit degeneration,muscle fiber denervation,reinnervation and atrophy,providing useful insights to help understand neuromuscular mechanisms associated with weakness and other functional deterioration post stroke.The CMAP scan experimental protocols and the applied processing methods are noninvasive,convenient,and automated,offering practical benefits for clinical application.
基金the National Science and Technology Innovation 2030-Major program of"Brain Science and Brain-Like Research"(2022ZD0211800)the National Natural Science Foundation of China(81971679,32020103007,32088101,and 21727806),the Ministry of Science and Technology(2018YFA0507600 and2017YFA0503600)+1 种基金theQidong-PKU SLS Innovation Fund(2016000663 and 2017000246)the National Key R&DProgram of China(2020AAA0105200).
文摘The back-propagating action potential(bpAP)is crucial for neuronal signal integration and synaptic plasticity in dendritic trees.Its properties(velocity and amplitude)can be affected by dendritic morphology.Due to limited spatial resolution,it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology,such as the dendrite diameter and branching pattern,using patch-clamp recording.By taking advantage of Optopatch,an all-optical electrophysiological method,we made detailed recordings of the real-time propagation of bpAPs in dendritic trees.We found that the velocity of bpAPs was not uniform in a single dendrite,and the bpAP velocity differed among distinct dendrites of the same neuron.The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated.In addition,when bpAPs passed through a dendritic branch point,their velocity decreased significantly.Similar to velocity,the amplitude of bpAPs was also positively correlated with dendritic diameter,and the attenuation patterns of bpAPs differed among different dendrites.Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results.These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs.The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology.These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology,to further illuminate the role of bpAPs in neuronal communication.
基金This work was supported by the National Natural Science Foundation of China(81870734)the Shanghai Municipal Government and ShanghaiTech University,China.
文摘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.
基金Supported by grant from Chinese NSFC "973" program
文摘Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson’s disease. Micro electrochemical carbon
基金Project supported by the National Natural Science Foundation of China(Grant No.62171312)the Tianjin Municipal Education Commission Scientific Research Project,China(Grant No.2020KJ114).
文摘Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.
文摘This paper derives rigorous statements concerning the propagation velocity of action potentials in axons. The authors use the Green’s function approach to approximate the action potential and find a relation between conduction velocity and the impulse profile. Computer simulations are used to bolster the analysis.
基金Scientific Committee Foundation(No.13102007) of Selcuk University,Konya,Turkey(to HB)
文摘Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative,anxiolytic,and analgesic effects.Dexketoprofen,which is used as an analgesic,is a nonselective nonsteroidal anti-inflammatory drug (NSAID).The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing.In this study,we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve.The isolated sciatic nerve from adult rats was transferred to a nerve chamber.The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods.Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10–9 to 10–5 M,and the CAPs were recorded for 5 and 10 minutes.The CAP parameters were calculated.Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group,i.e.,the group in which rats did not receive treatment.CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen.Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers;however,dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner.These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action.The experimental procedures were approved by the Necmettin Erbakan University on January 30,2013 (approval No.2013-024).
文摘Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.
文摘Repolarization heterogeneity(RH)is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram(ECG).Exceeding the physiologically based RH level is associated with appearance of life-threatening ventricular arrhythmias and sudden cardiac death.In this regard,an accurate and comprehensive evaluation of the degree of RH parameters is of importance for assessment of heart state and arrhythmic risk.This review is devoted to comprehensive consideration of RH phenomena in terms of electrophysiological processes underlying RH,cardiac electric field formation during ventricular repolarization,as well as clinical significance of RH and its reflection on ECG parameters.The formation of transmural,apicobasal,left-toright and anterior-posterior gradients of action potential durations and end of repolarization times resulting from the heterogenous distribution of repolarizing ion currents and action potential morphology throughout the heart ventricles,and the different sensitivity of myocardial cells in different ventricular regions to the action of pharmacological agents,temperature,frequency of stimulation,etc.,are being discussed.The review is focused on the fact that RH has different aspects–temporal and spatial,global and local;ECG reflection of various RH aspects and their clinical significance are being discussed.Strategies for comprehensive assessment of ventricular RH using different ECG indices reflecting various RH aspects are presented.
基金financially supported by the National Natural Science Foundation of China,No.81770990(to GCZ)Jiangsu Provincial Key Research and Development Program of China,No.BE2018628(to GCZ)+2 种基金Six Talent Peaks Project in Jiangsu Province of China,No.2019-WSW-141(to GCZ)Major Medicine Projects of Wuxi Health Commission of Jiangsu,China,No.Z201802(to DJX)Precision Medicine Projects of Wuxi Health Commission of Jiangsu,China,No.J202002(to GCZ)。
文摘Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple branches of an extratemporal segment.However,in the clinical treatment of facial nerve defects,allogeneic donors are limited.In this experiment,we exposed the left trunk and multiple branches of the extratemporal segment in six rhesus monkeys and dissected a gap of 25 mm to construct a monkey model of a whole left nerve defect.Six monkeys were randomly assigned to an autograft group or a xenogeneic acellular nerve graft group.In the autograft group,the 25-mm whole facial nerve defect was immediately bridged using an autogenous ipsilateral great auricular nerve,and in the xenogeneic acellular nerve graft group,this was done using a xenogeneic acellular nerve graft with trunk-branches.Examinations of facial symmetry,nerve-muscle electrophysiology,retrograde transport of labeled neuronal tracers,and morphology of the regenerated nerve and target muscle at 8 months postoperatively showed that the faces of the monkey appeared to be symmetrical in the static state and slightly asymmetrical during facial movement,and that they could actively close their eyelids completely.The degree of recovery from facial paralysis reached House-Brackmann grade II in both groups.Compound muscle action potentials were recorded and orbicularis oris muscles responded to electro-stimuli on the surgical side in each monkey.Fluoro Gold-labeled neurons could be detected in the facial nuclei on the injured side.Immunohistochemical staining showed abundant neurofilament-200-positive axons and soluble protein-100-positive Schwann cells in the regenerated nerves.A large number of mid-graft myelinated axons were observed via methylene blue staining and a transmission electron microscope.Taken together,our data indicate that xenogeneic acellular nerve grafts from minipigs are safe and effective for repairing whole facial nerve defects in rhesus monkeys,with an effect similar to that of autologous nerve transplantation.Thus,a xenogeneic acellular nerve graft may be a suitable choice for bridging a whole facial nerve defect if no other method is available.The study was approved by the Laboratory Animal Management Committee and the Ethics Review Committee of the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University,China(approval No.2018-D-1)on March 15,2018.
基金supported by a grant from the Natural Science Foundation of Hubei(2007ABA288)
文摘BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits.METHODS: Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups: sham-operated(SHAM) group(n=8), MI group(n=8) and MI with ramipril(RAM) group(n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confi rmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril(1 mg/kg per day) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fi brillation(VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student's t test and ANOVA were used for statistical analysis.RESULTS: VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks(2.6±0.8 vs. 12.4±2.9, P<0.05). Twelve weeks after MI, the duration of repolarization for 90%(APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI(258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7, P<0.05). However, the APD90 was not signif icantly different at 12 weeks before and after MI in the RAM group(P>0.05). Moreover, the transmural dispersion of repolarization(TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups(36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P<0.05). But the TDR was not signifi cantly different between the RAM and SHAM groups(18.7±6.2 vs. 24.9±8.7, P>0.05).CONCLUSION: Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.
文摘As hybrid cochlear implant devices are increasingly used for restoring hearing in patients with residual hearing, it is important to understand electrically evoked responses in cochleae having functional hair cells. To test the hypothesis that extracochlear electrical stimulation (EES) from sinusoidal current can provoke an auditory nerve response with normal frequency selectivity, the EES-evoked compound action potential(ECAP) was investigated in this study. Brief sinusoidal electrical currents, delivered via a round window electrode, were used to evoke ECAP. The ECAP waveform was observed to be the same as the acoustically evoked CAP(ACAP), except for a shorter latency. The input/output and intensity/latency functions of ACAPs and ECAPs were also similar. The maximum acoustic masking for both ACAP and ECAP occurred near probe frequencies. Since the masked tuning curve of a CAP reflects the frequency selectivity of neural excitation, these data demonstrate a highly specific activation of the auditory nerve, which would result in high degree of frequency selectivity. This frequency selectivity likely results from the cochlear traveling wave caused by electrically stimulated outer hair cells.
基金supported by a grant from Surface Project of Natural Science Foundation of Fujian Province(2008J0075)
文摘BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
