In this paper,we are concerned with a Hindmarsh-Rose(H-R) neuron model of fractional orders.By employing stability theory,we present some sufficient conditions ensuring the equilibrium of system to be stable.The simul...In this paper,we are concerned with a Hindmarsh-Rose(H-R) neuron model of fractional orders.By employing stability theory,we present some sufficient conditions ensuring the equilibrium of system to be stable.The simulations are provided to verify the theoretical results.展开更多
In recent years,discrete neuron and discrete neural network models have played an important role in the development of neural dynamics.This paper reviews the theoretical advantages of well-known discrete neuron models...In recent years,discrete neuron and discrete neural network models have played an important role in the development of neural dynamics.This paper reviews the theoretical advantages of well-known discrete neuron models,some existing discretized continuous neuron models,and discrete neural networks in simulating complex neural dynamics.It places particular emphasis on the importance of memristors in the composition of neural networks,especially their unique memory and nonlinear characteristics.The integration of memristors into discrete neural networks,including Hopfield networks and their fractional-order variants,cellular neural networks and discrete neuron models has enabled the study and construction of various neural models with memory.These models exhibit complex dynamic behaviors,including superchaotic attractors,hidden attractors,multistability,and synchronization transitions.Furthermore,the present paper undertakes an analysis of more complex dynamical properties,including synchronization,speckle patterns,and chimera states in discrete coupled neural networks.This research provides new theoretical foundations and potential applications in the fields of brain-inspired computing,artificial intelligence,image encryption,and biological modeling.展开更多
We propose a fractional-order improved Fitz Hugh–Nagumo(FHN)neuron model in terms of a generalized Caputo fractional derivative.Following the existence of a unique solution for the proposed model,we derive the numeri...We propose a fractional-order improved Fitz Hugh–Nagumo(FHN)neuron model in terms of a generalized Caputo fractional derivative.Following the existence of a unique solution for the proposed model,we derive the numerical solution using a recently proposed L1 predictor–corrector method.The given method is based on the L1-type discretization algorithm and the spline interpolation scheme.We perform the error and stability analyses for the given method.We perform graphical simulations demonstrating that the proposed FHN neuron model generates rich electrical activities of periodic spiking patterns,chaotic patterns,and quasi-periodic patterns.The motivation behind proposing a fractional-order improved FHN neuron model is that such a system can provide a more nuanced description of the process with better understanding and simulation of the neuronal responses by incorporating memory effects and non-local dynamics,which are inherent to many biological systems.展开更多
The firing of a neuron model is mainly affected by the following factors:the magnetic field,external forcing current,time delay,etc.In this paper,a new time-delayed electromagnetic field coupled dual Hindmarsh-Rose ne...The firing of a neuron model is mainly affected by the following factors:the magnetic field,external forcing current,time delay,etc.In this paper,a new time-delayed electromagnetic field coupled dual Hindmarsh-Rose neuron network model is constructed.A magnetically controlled threshold memristor is improved to represent the self-connected and the coupled magnetic fields triggered by the dynamic change of neuronal membrane potential for the adjacent neurons.Numerical simulation confirms that the coupled magnetic field can activate resting neurons to generate rich firing patterns,such as spiking firings,bursting firings,and chaotic firings,and enable neurons to generate larger firing amplitudes.The study also found that the strength of magnetic coupling in the neural network also affects the number of peaks in the discharge of bursting firing.Based on the existing medical treatment background of mental illness,the effects of time lag in the coupling process against neuron firing are studied.The results confirm that the neurons can respond well to external stimuli and coupled magnetic field with appropriate time delay,and keep periodic firing under a wide range of external forcing current.展开更多
Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and l...Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption characteristics.Analogous to the working mechanism of human brain,the SNN system transmits information through the spiking action of neurons.Therefore,artificial neurons are critical building blocks for constructing SNN in hardware.Memristors are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological neurons.Researchers have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional materials.Taking advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire model.In this review,the recent reports of artificial neurons based on memristive devices are discussed.In addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic devices.Finally,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.展开更多
The minimal two-dimensional model of bursting neuronal dynamics is used to study the influence of time-delay on the properties of synchronization of bursting neurons. Generic properties of bursting and dependence of t...The minimal two-dimensional model of bursting neuronal dynamics is used to study the influence of time-delay on the properties of synchronization of bursting neurons. Generic properties of bursting and dependence of the stability of synchronization on the time-lag and the strength of coupling are described, and compared with the two common types of synaptical coupling, i.e., time-delayed chemical and electrical synapses.展开更多
The purpose of this study was to establish a drug screening method for small molecules extracted from traditional Chinese medicines(TCM) that have neuronal differentiation promoting effects, using P19 embryonic carcin...The purpose of this study was to establish a drug screening method for small molecules extracted from traditional Chinese medicines(TCM) that have neuronal differentiation promoting effects, using P19 embryonic carcinoma cell as a cell-based model. First, the constructed plasmid(p Tα1-Luc) was transfected into P19 cells to establish a screening model. Second, several TCMs were screened using the established model and all-trans-retinoic acid as a positive control. Finally, the underlying molecular mechanism was explored using immunofluorescence staining, q T-PCR, and Western blot analysis. Our results indicated that the drug screen model was established successfully and that both honokiol and hyperoside induced P19 differentiation into neurons, with the possible molecular mechanism being modulating the Wnt signaling pathway. In conclusion, the drug screening model developed in the present study provides a rapid, cell-based screening platform for identifying natural compounds with neuronal differentiation effects.展开更多
AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimic...AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimicked by repeating administrations of TNBS.Tissue samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation.The means of the ulcerated area were measured to evaluate the macroscopic mu-cosal damage.The density of myenteric neurons was determined on whole mounts by Hu C/Hu D immunohistochemistry.Heme oxygenase-1(HO-1)expression was evaluated by molecular biological techniques.RESULTS:TNBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental period.The widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration.After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed area.HO-1 m RNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined.Nevertheless,the HO-1protein up-regulation after the second TNBS treatment proved to be transient.Following the third treatment HO-1 protein expression could not be detected.CONCLUSION:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage.The persistent up-regulation of HO-1 m RNA expression may correlate with this.展开更多
Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:...Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.展开更多
In the presence of Gaussian white noise,we study the properties of voltage-controlled oscillator neuronmodel and discuss the effects of the additive and multiplicative noise.It is found that the additive noise can acc...In the presence of Gaussian white noise,we study the properties of voltage-controlled oscillator neuronmodel and discuss the effects of the additive and multiplicative noise.It is found that the additive noise can accelerate andcounterwork the firing of neuron,which depends on the value of central frequency of neuron itself,while multiplicativenoise can induce the continuous change or mutation of membrane potential.展开更多
Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which ca...Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.展开更多
Alzheimer’s disease（AD）,the main cause of dementia,is defined by the combined presence of amyloid-b（Ab）deposition and abnormal tau aggregation[1].Experimental models are critical to obtain a better understanding ...Alzheimer’s disease（AD）,the main cause of dementia,is defined by the combined presence of amyloid-b（Ab）deposition and abnormal tau aggregation[1].Experimental models are critical to obtain a better understanding of AD pathogenesis,and to evaluate the potential of novel therapeutic approaches.The most commonly used AD展开更多
The present study revealed the stimulatory effects of NMDA on intracellular ca 2+ concentration in rat dorsal root ganglion (DRG) neurons. Fura 3/AM, an intracellular calcium fluorescent indicator was used to monitor ...The present study revealed the stimulatory effects of NMDA on intracellular ca 2+ concentration in rat dorsal root ganglion (DRG) neurons. Fura 3/AM, an intracellular calcium fluorescent indicator was used to monitor the fluctuation of 〔ca 2+ 〕 i. Here we present the evidence that (1) Confocal microscopy resolved the cells of three different sizes, based on which a cell diameter distribution histogram was drawn. The fluorescence signals originated from the cells of different sizes, small size (diameter<30μm), medium size (diameter between 30 to 50μm),and large size (diameter>50μm); presumably intracellular Ca 2+ concentration was different in the cells of different sizes. (2) The time related variation of fluorescence intensity was observed. In particular, the fluorescence intensity in 0 Ca 2+ bath solution was affected by the application of high ca 2+ solution. (3) In 0 ca 2+ bath solution the intracellular Ca 2+ concentration nonlinear properties of distinct diameter cells was described. (4) A kind of SETAR model was fitted with a medium sized cell.(5)The residuals from the fitted model were tested to see whether they were plausibly Gaussian. These findings indicated that in distinct types of cells intracellular Ca 2+ concentration had different characteristics in different DRG neurons, and contributed to different functions of these neurons. Besides, the established threshold autoregressive model can share intracellular ca 2+ with the main nonlinear kinetic展开更多
Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain...Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain impact,the injury region in axons exhibits significant longitudinal strain;and in a rat model of spinal cord injury,the most severe axonal injury is located in the largest strain region.Stretching may result in microstructural changes in neural tissue and further leading to abnormal electrophysiological function.Hence,it is of great importance to understand the coupled mechanoelectricalbehaviors of neurons under stretching.In spite of significant experimental efforts,the underlying mechanism remains elusive,more works are needed to provide a detailed description of the process that leads to the observed phenomena.Mathematical modeling is a powerful tool that offers a quantitative description of the underlying mechanism of an observed biological phenomenon,including mechanical and electrophysiological behaviors of neurons.Thus,we developed a mechanoelectrical coupling model of neurons under stretching in this study.Mathematical model The mathematical model consists of three submodels,i.e.,the mechanical submodel,the mechanoelectrical coupling submodel and the electrophysiological submodel.The mechanical submodel deals with the relationship between stretching and the deformation of axons,which has specially considered the plastic deformation of axons.The electrophysiological submodel characterizes the feature of neuronal action potential(AP),which is based on the classical H-H model and the cable theory.The mechanoelectrical coupling submodel links the mechanical and electrophysiological submodels through strain-induced equivalent circuit parameter alteration and ion channel injury.Besides,we have discussed a more general deformation condition,where an expanded model coupling the axonal deformation and electrophysiology alteration was explored.As the most essential parameters in an electrophysiological assessment,the amplitude of the AP,the neuronal firing frequency and the electrophysiological signal conduction velocity,which could be affected by stretching,were used as outputs of the model.Results&discussion To understand the mechanoelectrical coupling of neurons under stretching,we developed a mechanoelectrical coupling model.To verify the model,we simulated a slow stretching on an axon following the experimental study in the literature,we observed that as the strain increases,the peak AP declines faster,which is consistent with the experimental data.Moreover,the reduced AP cannot be restored to the original peak,implying that the damage is irreversible.The simulation results also predict that strain induces a more frequent neuronal firing and a faster conduction.In a realistic situation,in addition to stretching,the loading condition is very complicated,which may induce complex axonal deformation(e.g., necking and swelling along the axons).We also simulated such necking deformation impairment and observed that the AP amplitude decreases at the necking region and recovers after that,indicating a blockage of the AP;and the conduction velocity decreases with the increase in deformation degree.Conclusions In this study,we developed a mechanoelectrical coupling model of neurons under stretching with consideration of axonal plastic deformation.With the model,we found that the effect of mechanical loading on electrophysiology mainly manifests as decreased membrane AP amplitude,a more frequent neuronal firing and a faster electrophysiological signal conduction.The model predicts not only stretch-induced injury but also a more gene ral necking deformation case,which may someday be revealed in future by experiments,providing a reference for the prediction and regulation of neuronal function under mechanical loadings.展开更多
Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to ...Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to simulate CN neurons will be a feasible way. Methods: Based on the initial model mentioned in the previous study, we proposed an improved CN model in MATLAB R2012b. Results: By modifying the parameters of the model we found the interchanges among "primary-like", "chopper",and "onset" response patterns. Furthermore, we simulated the "pauser" response pattern by adding an extra input in our model. Conclusion: The results indicate that the synaptic integrations and the input modes can give rise to different characteristics of CN neurons, which eventually determine the response patterns of CN neurons.展开更多
The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders.Rodent models of brain diseases have spurred understanding...The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders.Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology.iPSC derived neurons,or other neural cell types,provide the ability to access pathology in cells derived directly from a patient＇s blood sample or skin biopsy where availability of brain tissue is limiting.Thus,utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future.Many brain diseases across the spectrum of neurodevelopment,neurodegenerative and neuropsychiatric are being approached by iPSC models.The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells.In this mini-review,the importance of iPSC cell models validated for pluripotency,germline competency and function assessments is discussed.Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.展开更多
Sim and Forger have proposed a mathematical model of circadian pacemaker neurons in the suprachiasmatic nucleus (SCN). This model, which has been formulated on the Hodgkin-Huxley mo-del, is described by a system of no...Sim and Forger have proposed a mathematical model of circadian pacemaker neurons in the suprachiasmatic nucleus (SCN). This model, which has been formulated on the Hodgkin-Huxley mo-del, is described by a system of nonlinear ordinary differential equations. An important feature of the SCN neurons observed in electrophysiological recording is spontaneous repetitive spiking, which is reproduced using this model. In the present study, numerical simulation analysis of this model was performed to evaluate variations in two system parameters of this model: the maximal conductance of calcium current (gCa) and the maximal conductance of sodium current (gNa). Simulation results revealed the spontaneous repetitive spiking states of the model in the (gCa, gNa)-pa-rameter space.展开更多
A spike response model(SRM)based on the spikes generator circuit(SGC)of adaptive fuzzy spiking neurons(AFSNs)is developed.The SRM is simulated in MatlabTM environment.The proposed model is applied to a configuration o...A spike response model(SRM)based on the spikes generator circuit(SGC)of adaptive fuzzy spiking neurons(AFSNs)is developed.The SRM is simulated in MatlabTM environment.The proposed model is applied to a configuration of a fuzzy exclusive or(fuzzy XOR)operator,as an illustrative example.A description of the comparison of AFSNs with other similar methods is given.The novel method of the AFSNs is used to determine the value of the weights or parameters of the fuzzy XOR,first with dynamic weights or self-tuning parameters that adapt continuously,then with fixed weights obtained after training,finally with fixed weights and a dynamic gain or self-tuning gain for a fine adjustment of amplitude.展开更多
Memristors are extensively used to estimate the external electromagnetic stimulation and synapses for neurons.In this paper,two distinct scenarios,i.e.,an ideal memristor serves as external electromagnetic stimulation...Memristors are extensively used to estimate the external electromagnetic stimulation and synapses for neurons.In this paper,two distinct scenarios,i.e.,an ideal memristor serves as external electromagnetic stimulation and a locally active memristor serves as a synapse,are formulated to investigate the impact of a memristor on a two-dimensional Hindmarsh-Rose neuron model.Numerical simulations show that the neuronal models in different scenarios have multiple burst firing patterns.The introduction of the memristor makes the neuronal model exhibit complex dynamical behaviors.Finally,the simulation circuit and DSP hardware implementation results validate the physical mechanism,as well as the reliability of the biological neuron model.展开更多
基金National Natural Science Foundation of China(No.61174155No.11032009)
文摘In this paper,we are concerned with a Hindmarsh-Rose(H-R) neuron model of fractional orders.By employing stability theory,we present some sufficient conditions ensuring the equilibrium of system to be stable.The simulations are provided to verify the theoretical results.
基金supported by the Natural Science Foundation of Hunan Province(Grant No.2025JJ50368)the Scientific Research Fund of Hunan Provincial Education Department(Grant No.24A0248)the Guiding Science and Technology Plan Project of Changsha City(Grant No.kzd2501129)。
文摘In recent years,discrete neuron and discrete neural network models have played an important role in the development of neural dynamics.This paper reviews the theoretical advantages of well-known discrete neuron models,some existing discretized continuous neuron models,and discrete neural networks in simulating complex neural dynamics.It places particular emphasis on the importance of memristors in the composition of neural networks,especially their unique memory and nonlinear characteristics.The integration of memristors into discrete neural networks,including Hopfield networks and their fractional-order variants,cellular neural networks and discrete neuron models has enabled the study and construction of various neural models with memory.These models exhibit complex dynamic behaviors,including superchaotic attractors,hidden attractors,multistability,and synchronization transitions.Furthermore,the present paper undertakes an analysis of more complex dynamical properties,including synchronization,speckle patterns,and chimera states in discrete coupled neural networks.This research provides new theoretical foundations and potential applications in the fields of brain-inspired computing,artificial intelligence,image encryption,and biological modeling.
文摘We propose a fractional-order improved Fitz Hugh–Nagumo(FHN)neuron model in terms of a generalized Caputo fractional derivative.Following the existence of a unique solution for the proposed model,we derive the numerical solution using a recently proposed L1 predictor–corrector method.The given method is based on the L1-type discretization algorithm and the spline interpolation scheme.We perform the error and stability analyses for the given method.We perform graphical simulations demonstrating that the proposed FHN neuron model generates rich electrical activities of periodic spiking patterns,chaotic patterns,and quasi-periodic patterns.The motivation behind proposing a fractional-order improved FHN neuron model is that such a system can provide a more nuanced description of the process with better understanding and simulation of the neuronal responses by incorporating memory effects and non-local dynamics,which are inherent to many biological systems.
基金Project supported by the National Natural Science Foundation of China(Grant No.61873186)。
文摘The firing of a neuron model is mainly affected by the following factors:the magnetic field,external forcing current,time delay,etc.In this paper,a new time-delayed electromagnetic field coupled dual Hindmarsh-Rose neuron network model is constructed.A magnetically controlled threshold memristor is improved to represent the self-connected and the coupled magnetic fields triggered by the dynamic change of neuronal membrane potential for the adjacent neurons.Numerical simulation confirms that the coupled magnetic field can activate resting neurons to generate rich firing patterns,such as spiking firings,bursting firings,and chaotic firings,and enable neurons to generate larger firing amplitudes.The study also found that the strength of magnetic coupling in the neural network also affects the number of peaks in the discharge of bursting firing.Based on the existing medical treatment background of mental illness,the effects of time lag in the coupling process against neuron firing are studied.The results confirm that the neurons can respond well to external stimuli and coupled magnetic field with appropriate time delay,and keep periodic firing under a wide range of external forcing current.
基金supported financially by the fund from the Ministry of Science and Technology of China(Grant No.2019YFB2205100)the National Science Fund for Distinguished Young Scholars(No.52025022)+3 种基金the National Nature Science Foundation of China(Grant Nos.U19A2091,62004016,51732003,52072065,1197407252272140 and 52372137)the‘111’Project(Grant No.B13013)the Fundamental Research Funds for the Central Universities(Nos.2412023YQ004 and 2412022QD036)the funding from Jilin Province(Grant Nos.20210201062GX,20220502002GH,20230402072GH,20230101017JC and 20210509045RQ)。
文摘Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption characteristics.Analogous to the working mechanism of human brain,the SNN system transmits information through the spiking action of neurons.Therefore,artificial neurons are critical building blocks for constructing SNN in hardware.Memristors are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological neurons.Researchers have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional materials.Taking advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire model.In this review,the recent reports of artificial neurons based on memristive devices are discussed.In addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic devices.Finally,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.
基金Project supported by the Serbian Ministry of Science(Grant Nos.171017 and 174010)
文摘The minimal two-dimensional model of bursting neuronal dynamics is used to study the influence of time-delay on the properties of synchronization of bursting neurons. Generic properties of bursting and dependence of the stability of synchronization on the time-lag and the strength of coupling are described, and compared with the two common types of synaptical coupling, i.e., time-delayed chemical and electrical synapses.
基金supported by the China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs(No.2009ZX09302)National Natural Science Foundation of China(No.81271338)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20130096110011)
文摘The purpose of this study was to establish a drug screening method for small molecules extracted from traditional Chinese medicines(TCM) that have neuronal differentiation promoting effects, using P19 embryonic carcinoma cell as a cell-based model. First, the constructed plasmid(p Tα1-Luc) was transfected into P19 cells to establish a screening model. Second, several TCMs were screened using the established model and all-trans-retinoic acid as a positive control. Finally, the underlying molecular mechanism was explored using immunofluorescence staining, q T-PCR, and Western blot analysis. Our results indicated that the drug screen model was established successfully and that both honokiol and hyperoside induced P19 differentiation into neurons, with the possible molecular mechanism being modulating the Wnt signaling pathway. In conclusion, the drug screening model developed in the present study provides a rapid, cell-based screening platform for identifying natural compounds with neuronal differentiation effects.
基金Supported by Hungarian Scientific Research Fund,No.OTKA PD 108309(to Bódi N)European Union and the State of Hungaryco-financed by the European Social Fund in the frame-work of TáMOP 4.2.4.A/2-11/1-2012-0001"National Excellence Program"
文摘AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimicked by repeating administrations of TNBS.Tissue samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation.The means of the ulcerated area were measured to evaluate the macroscopic mu-cosal damage.The density of myenteric neurons was determined on whole mounts by Hu C/Hu D immunohistochemistry.Heme oxygenase-1(HO-1)expression was evaluated by molecular biological techniques.RESULTS:TNBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental period.The widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration.After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed area.HO-1 m RNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined.Nevertheless,the HO-1protein up-regulation after the second TNBS treatment proved to be transient.Following the third treatment HO-1 protein expression could not be detected.CONCLUSION:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage.The persistent up-regulation of HO-1 m RNA expression may correlate with this.
基金CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:31970510Young Elite Scientist Sponsorship Program by CAST,Grant/Award Number:2019QNRC001。
文摘Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.
基金National Natural Science Foundation of China under Grant No.30600122Natural Science Foundation of Guangdong Province of China under Grant No.06025073the Natural Science Foundation of South China University of Technology under Grant No.B14-E5050200
文摘In the presence of Gaussian white noise,we study the properties of voltage-controlled oscillator neuronmodel and discuss the effects of the additive and multiplicative noise.It is found that the additive noise can accelerate andcounterwork the firing of neuron,which depends on the value of central frequency of neuron itself,while multiplicativenoise can induce the continuous change or mutation of membrane potential.
基金supported by grants from the Spanish Ministry of Economy and Competitivenessthe European Regional Development Fund 2007-2013(BFU2014-56300-P)+4 种基金the Xunta de Galicia(GPC2014/030)supported by a grant from the Xunta de Galicia(2016-PG008)a grant from the crowdfunding platform Precipita(FECYTSpanish Ministry of Economy and Competitivenessgrant number 2017-CP081)
文摘Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.
基金partly supported by grants from the National Key Research and Development Program of China(2016YFA0100900)the International S&T Cooperation Program of China(2015DFG32740)the National Natural Science Foundation of China(81571711 and 81425015)
文摘Alzheimer’s disease（AD）,the main cause of dementia,is defined by the combined presence of amyloid-b（Ab）deposition and abnormal tau aggregation[1].Experimental models are critical to obtain a better understanding of AD pathogenesis,and to evaluate the potential of novel therapeutic approaches.The most commonly used AD
文摘The present study revealed the stimulatory effects of NMDA on intracellular ca 2+ concentration in rat dorsal root ganglion (DRG) neurons. Fura 3/AM, an intracellular calcium fluorescent indicator was used to monitor the fluctuation of 〔ca 2+ 〕 i. Here we present the evidence that (1) Confocal microscopy resolved the cells of three different sizes, based on which a cell diameter distribution histogram was drawn. The fluorescence signals originated from the cells of different sizes, small size (diameter<30μm), medium size (diameter between 30 to 50μm),and large size (diameter>50μm); presumably intracellular Ca 2+ concentration was different in the cells of different sizes. (2) The time related variation of fluorescence intensity was observed. In particular, the fluorescence intensity in 0 Ca 2+ bath solution was affected by the application of high ca 2+ solution. (3) In 0 ca 2+ bath solution the intracellular Ca 2+ concentration nonlinear properties of distinct diameter cells was described. (4) A kind of SETAR model was fitted with a medium sized cell.(5)The residuals from the fitted model were tested to see whether they were plausibly Gaussian. These findings indicated that in distinct types of cells intracellular Ca 2+ concentration had different characteristics in different DRG neurons, and contributed to different functions of these neurons. Besides, the established threshold autoregressive model can share intracellular ca 2+ with the main nonlinear kinetic
基金financially supported by the National Natural Science Foundation of China ( 11522219, 11532009)the Projects of International ( Regional) Cooperation and Exchanges of NSFC ( 11761161004)+3 种基金the Natural Science Basic Research Plan in Shaanxi Province of China ( 2017JM1026,2017JM8097)the National Project Cultivating Foundation of Xi’an Medical University ( 2017GJFY23)Young Talent Support Plan of Shaanxi Provincethe China Postdoctoral Science Foundation ( 2018M631141,2018M631173)
文摘Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain impact,the injury region in axons exhibits significant longitudinal strain;and in a rat model of spinal cord injury,the most severe axonal injury is located in the largest strain region.Stretching may result in microstructural changes in neural tissue and further leading to abnormal electrophysiological function.Hence,it is of great importance to understand the coupled mechanoelectricalbehaviors of neurons under stretching.In spite of significant experimental efforts,the underlying mechanism remains elusive,more works are needed to provide a detailed description of the process that leads to the observed phenomena.Mathematical modeling is a powerful tool that offers a quantitative description of the underlying mechanism of an observed biological phenomenon,including mechanical and electrophysiological behaviors of neurons.Thus,we developed a mechanoelectrical coupling model of neurons under stretching in this study.Mathematical model The mathematical model consists of three submodels,i.e.,the mechanical submodel,the mechanoelectrical coupling submodel and the electrophysiological submodel.The mechanical submodel deals with the relationship between stretching and the deformation of axons,which has specially considered the plastic deformation of axons.The electrophysiological submodel characterizes the feature of neuronal action potential(AP),which is based on the classical H-H model and the cable theory.The mechanoelectrical coupling submodel links the mechanical and electrophysiological submodels through strain-induced equivalent circuit parameter alteration and ion channel injury.Besides,we have discussed a more general deformation condition,where an expanded model coupling the axonal deformation and electrophysiology alteration was explored.As the most essential parameters in an electrophysiological assessment,the amplitude of the AP,the neuronal firing frequency and the electrophysiological signal conduction velocity,which could be affected by stretching,were used as outputs of the model.Results&discussion To understand the mechanoelectrical coupling of neurons under stretching,we developed a mechanoelectrical coupling model.To verify the model,we simulated a slow stretching on an axon following the experimental study in the literature,we observed that as the strain increases,the peak AP declines faster,which is consistent with the experimental data.Moreover,the reduced AP cannot be restored to the original peak,implying that the damage is irreversible.The simulation results also predict that strain induces a more frequent neuronal firing and a faster conduction.In a realistic situation,in addition to stretching,the loading condition is very complicated,which may induce complex axonal deformation(e.g., necking and swelling along the axons).We also simulated such necking deformation impairment and observed that the AP amplitude decreases at the necking region and recovers after that,indicating a blockage of the AP;and the conduction velocity decreases with the increase in deformation degree.Conclusions In this study,we developed a mechanoelectrical coupling model of neurons under stretching with consideration of axonal plastic deformation.With the model,we found that the effect of mechanical loading on electrophysiology mainly manifests as decreased membrane AP amplitude,a more frequent neuronal firing and a faster electrophysiological signal conduction.The model predicts not only stretch-induced injury but also a more gene ral necking deformation case,which may someday be revealed in future by experiments,providing a reference for the prediction and regulation of neuronal function under mechanical loadings.
基金National Natural Science Foundation of Chinagrant number:31171059
文摘Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to simulate CN neurons will be a feasible way. Methods: Based on the initial model mentioned in the previous study, we proposed an improved CN model in MATLAB R2012b. Results: By modifying the parameters of the model we found the interchanges among "primary-like", "chopper",and "onset" response patterns. Furthermore, we simulated the "pauser" response pattern by adding an extra input in our model. Conclusion: The results indicate that the synaptic integrations and the input modes can give rise to different characteristics of CN neurons, which eventually determine the response patterns of CN neurons.
文摘The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders.Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology.iPSC derived neurons,or other neural cell types,provide the ability to access pathology in cells derived directly from a patient＇s blood sample or skin biopsy where availability of brain tissue is limiting.Thus,utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future.Many brain diseases across the spectrum of neurodevelopment,neurodegenerative and neuropsychiatric are being approached by iPSC models.The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells.In this mini-review,the importance of iPSC cell models validated for pluripotency,germline competency and function assessments is discussed.Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.
文摘Sim and Forger have proposed a mathematical model of circadian pacemaker neurons in the suprachiasmatic nucleus (SCN). This model, which has been formulated on the Hodgkin-Huxley mo-del, is described by a system of nonlinear ordinary differential equations. An important feature of the SCN neurons observed in electrophysiological recording is spontaneous repetitive spiking, which is reproduced using this model. In the present study, numerical simulation analysis of this model was performed to evaluate variations in two system parameters of this model: the maximal conductance of calcium current (gCa) and the maximal conductance of sodium current (gNa). Simulation results revealed the spontaneous repetitive spiking states of the model in the (gCa, gNa)-pa-rameter space.
文摘A spike response model(SRM)based on the spikes generator circuit(SGC)of adaptive fuzzy spiking neurons(AFSNs)is developed.The SRM is simulated in MatlabTM environment.The proposed model is applied to a configuration of a fuzzy exclusive or(fuzzy XOR)operator,as an illustrative example.A description of the comparison of AFSNs with other similar methods is given.The novel method of the AFSNs is used to determine the value of the weights or parameters of the fuzzy XOR,first with dynamic weights or self-tuning parameters that adapt continuously,then with fixed weights obtained after training,finally with fixed weights and a dynamic gain or self-tuning gain for a fine adjustment of amplitude.
基金supported by the National Natural Science Foundation of China(Grant No.62061014)Technological Innovation Projects in the Field of Artificial Intelligence in Liaoning province(Grant No.2023JH26/10300011)Basic Scientific Research Projects in Department of Education of Liaoning Province(Grant No.JYTZD2023021).
文摘Memristors are extensively used to estimate the external electromagnetic stimulation and synapses for neurons.In this paper,two distinct scenarios,i.e.,an ideal memristor serves as external electromagnetic stimulation and a locally active memristor serves as a synapse,are formulated to investigate the impact of a memristor on a two-dimensional Hindmarsh-Rose neuron model.Numerical simulations show that the neuronal models in different scenarios have multiple burst firing patterns.The introduction of the memristor makes the neuronal model exhibit complex dynamical behaviors.Finally,the simulation circuit and DSP hardware implementation results validate the physical mechanism,as well as the reliability of the biological neuron model.
