Human mirror neuron system and its plasticity

The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.

Electroencephalogram evidence for the activation of human mirror neuron system during the observation of intransitive shadow and line drawing actions

Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system during the observation of intransitive movements by shadows and line drawings of hands. This study examined the suppression of electroencephalography mu waves （8-13 Hz） induced by observation of stimuli in 18 healthy students. Three stimuli were used： real hand actions, hand shadow actions and actions made by line drawings of hands. The results showed significant desynchronization of the mu rhythm （＂mu suppression＂） across the sensodmotor cortex （recorded at C3, Cz and C4）, the frontal cortex （recorded at F3, Fz and F4） and the central and right posterior parietal cortex （recorded at Pz and P4） under all three conditions. Our experimental findings suggest that the observation of ＂impoverished hand actions＂, such as intransitive movements of shadows and line drawings of hands, is able to activate widespread cortical areas related to the putative human mirror neuron system.

Synchronization in the Uncoupled Neuron System

Using the model of Hindmarsh Rose neurons, we study the synchronous behavior of the firing patterns in an uncoupled cell system. In this work, the membrane current Iext is selected as a controllable parameter, whose initial values for all N cells are set to be near one of the bifurcation points randomly. It is found that the system will show un-synchronous state when the external stimuli is absent, otherwise, full synchrony will appear, even though without any coupling connection among these N neurons, indicating the occurrence of uncoupled synchrony. Moreover, similar behavior could also be observed when these neurons are set to be near other bifurcation points. The synchronous error is calculated for discussing this uncoupled synehrony behavior. Finally, we find that such synchrony may have some inherent relevance with the decrease of phase difference between different cells. Our results suggest that biological neuron systems may achieve an effective response to external feeble stimulus by the mode of uncoupled synchrony instead of only by the coupled scheme.

Neural Correlates of Developmental Coordination Disorder: The Mirror Neuron System Hypothesis

Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into adulthood, negatively impacting daily life in school, work, and social domains. A better understanding of the neural correlates of motor and imitation impairments in DCD holds the potential for informing development of treatment approaches to address these impairments. Although the disorder is assumed to be of neurological origin, little is known of the brain-based etiology of DCD. In recent years the discovery of a fronto-parietal circuit—known as the mirror neuron system—has enabled researchers to better understand imitation, general motor functions, and aspects of social cognition. Given its involvement in imitation and other motor functions, we propose that dysfunction in the mirror neuron system may underlie the characteristic impairments of DCD. We review literature pertaining to the mirror neuron system and develop a theory of disordered mirror neuron functioning in DCD. Finally, we review the limited neuroimaging literature available on neural correlates of DCD and show that the findings from those investigations are congruent with a mirror neuron system theory of DCD. Future research in this population should be designed to investigate specifically mirror neuron regions in individuals with DCD during skilled motor tasks and imitation in particular.

Synchronization and firing mode transition of two neurons in a bilateral auditory system driven by a high–low frequency signal

The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron system.Two piezoelectric sensing neurons are coupled by a parallel circuit consisting of a Josephson junction and a linear resistor,and a binaural auditory system is established.Considering the non-singleness of external sound sources,the high–low frequency signal is used as the input signal to study the firing mode transition and synchronization of this system.It is found that the angular frequency of the high–low frequency signal is a key factor in determining whether the dynamic behaviors of two coupled neurons are synchronous.When they are in synchronization at a specific angular frequency,the changes in physical parameters of the input signal and the coupling strength between them will not destroy their synchronization.In addition,the firing mode of two coupled auditory neurons in synchronization is affected by the characteristic parameters of the high–low frequency signal rather than the coupling strength.The asynchronous dynamic behavior and variations in firing modes will harm the auditory system.These findings could help determine the causes of hearing loss and devise functional assistive devices for patients.

Exercise-induced adaptation of neurons in the vertebrate locomotor system

Vertebrate neurons are highly dynamic cells that undergo several alterations in their functioning and physiologies in adaptation to various external stimuli.In particular,how these neurons respond to physical exercise has long been an area of active research.Studies of the vertebrate locomotor system’s adaptability suggest multiple mechanisms are involved in the regulation of neuronal activity and properties during exercise.In this brief review,we highlight recent results and insights from the field with a focus on the following mechanisms:(a)alterations in neuronal excitability during acute exercise;(b)alterations in neuronal excitability after chronic exercise;(c)exercise-induced changes in neuronal membrane properties via modulation of ion channel activity;(d)exercise-enhanced dendritic plasticity;and(e)exercise-induced alterations in neuronal gene expression and protein synthesis.Our hope is to update the community with a cellular and molecular understanding of the recent mechanisms underlying the adaptability of the vertebrate locomotor system in response to both acute and chronic physical exercise.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Effects of electric field on vibrational resonances in Hindmarsh-Rose neuronal systems for signal detection

Changes in the concentration of charged ions in neurons can generate induced electric fields,which can further modulate cell membrane potential.In this paper,Fourier coefficients are used to investigate the effect of electric field on vibrational resonance for signal detection in a single neuron model and a bidirectionally coupled neuron model,respectively.The study found that the internal electric field weakens vibrational resonance by changing two factors,membrane potential and phase-locked mode,while the periodic external electric field of an appropriate frequency significantly enhances the vibrational resonance,suggesting that the external electric field may play a constructive role in the detection of weak signals in the brain and neuronal systems.Furthermore,when the coupling of two neurons is considered,the effect of the electric field on the vibrational resonance is similar to that of a single neuron.The paper also illustrates the effect of electric field coupling on vibrational resonance.This study may provide a new theoretical basis for understanding information encoding and transmission in neurons.

Inhibitory effect induced by fractional Gaussian noise in neuronal system

We discover a phenomenon of inhibition effect induced by fractional Gaussian noise in a neuronal system. Firstly,essential properties of fractional Brownian motion(fBm) and generation of fractional Gaussian noise(fGn) are presented,and representative sample paths of fBm and corresponding spectral density of fGn are discussed at different Hurst indexes.Next, we consider the effect of fGn on neuronal firing, and observe that neuronal firing decreases first and then increases with increasing noise intensity and Hurst index of fGn by studying the time series evolution. To further quantify the inhibitory effect of fGn, by introducing the average discharge rate, we investigate the effects of noise and external current on neuronal firing, and find the occurrence of inhibitory effect about noise intensity and Hurst index of f Gn at a certain level of current. Moreover, the inhibition effect is not easy to occur when the noise intensity and Hurst index are too large or too small. In view of opposite action mechanism compared with stochastic resonance, this suppression phenomenon is called inverse stochastic resonance(ISR). Finally, the inhibitory effect induced by fGn is further verified based on the inter-spike intervals(ISIs) in the neuronal system. Our work lays a solid foundation for future study of non-Gaussian-type noise on neuronal systems.

In vivo imaging of the neuronal response to spinal cord injury:a narrative review

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.

Advances in memristor based artificial neuron fabrication-materials,models,and applications

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.

Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

How do neurons age?A focused review on the aging of the microtubular cytoskeleton

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain regions that are worthy of further investigation. Additionally, longitudinal studies of neuronal/cytoskeletal aging should also investigate whether these age-related changes contribute not just to vulnerability to disease but also to the decline in nervous system function and behavioral output that all organisms experience. This will highlight the utility, if any, of cytoskeletal fortification for the promotion of healthy neuronal aging and potential protection against age-related neurodegenerative disease. This review seeks to summarize what is currently known about the physiological aging of the neuron and microtubular cytoskeleton in the hope of uncovering mechanisms underpinning age-related risk to disease.

Dynamical behaviors in discrete memristor-coupled small-world neuronal networks

The brain is a complex network system in which a large number of neurons are widely connected to each other and transmit signals to each other.The memory characteristic of memristors makes them suitable for simulating neuronal synapses with plasticity.In this paper,a memristor is used to simulate a synapse,a discrete small-world neuronal network is constructed based on Rulkov neurons and its dynamical behavior is explored.We explore the influence of system parameters on the dynamical behaviors of the discrete small-world network,and the system shows a variety of firing patterns such as spiking firing and triangular burst firing when the neuronal parameterαis changed.The results of a numerical simulation based on Matlab show that the network topology can affect the synchronous firing behavior of the neuronal network,and the higher the reconnection probability and number of the nearest neurons,the more significant the synchronization state of the neurons.In addition,by increasing the coupling strength of memristor synapses,synchronization performance is promoted.The results of this paper can boost research into complex neuronal networks coupled with memristor synapses and further promote the development of neuroscience.

The physiological role of the unfolded protein response in the nervous system

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

Dynamics and synchronization in a memristor-coupled discrete heterogeneous neuron network considering noise

Research on discrete memristor-based neural networks has received much attention.However,current research mainly focuses on memristor–based discrete homogeneous neuron networks,while memristor-coupled discrete heterogeneous neuron networks are rarely reported.In this study,a new four-stable discrete locally active memristor is proposed and its nonvolatile and locally active properties are verified by its power-off plot and DC V–I diagram.Based on two-dimensional(2D)discrete Izhikevich neuron and 2D discrete Chialvo neuron,a heterogeneous discrete neuron network is constructed by using the proposed discrete memristor as a coupling synapse connecting the two heterogeneous neurons.Considering the coupling strength as the control parameter,chaotic firing,periodic firing,and hyperchaotic firing patterns are revealed.In particular,multiple coexisting firing patterns are observed,which are induced by different initial values of the memristor.Phase synchronization between the two heterogeneous neurons is discussed and it is found that they can achieve perfect synchronous at large coupling strength.Furthermore,the effect of Gaussian white noise on synchronization behaviors is also explored.We demonstrate that the presence of noise not only leads to the transition of firing patterns,but also achieves the phase synchronization between two heterogeneous neurons under low coupling strength.

Role of lipids in the control of autophagy and primary cilium signaling in neurons

The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.

Fractional-order heterogeneous memristive Rulkov neuronal network and its medical image watermarking application

This article proposes a novel fractional heterogeneous neural network by coupling a Rulkov neuron with a Hopfield neural network(FRHNN),utilizing memristors for emulating neural synapses.The study firstly demonstrates the coexistence of multiple firing patterns through phase diagrams,Lyapunov exponents(LEs),and bifurcation diagrams.Secondly,the parameter related firing behaviors are described through two-parameter bifurcation diagrams.Subsequently,local attraction basins reveal multi-stability phenomena related to initial values.Moreover,the proposed model is implemented on a microcomputer-based ARM platform,and the experimental results correspond to the numerical simulations.Finally,the article explores the application of digital watermarking for medical images,illustrating its features of excellent imperceptibility,extensive key space,and robustness against attacks including noise and cropping.

Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.