Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes tha...Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes that myelinate central nervous system （CNS） axons. Evidence suggests, however, that they have other functions, besides differentiating into oligodendrocytes. Most notably, the OPCs/NG2 cells are uni- formly distributed in grey matter as well as in white matter, which matches poorly with the distribution of myelinating oligodendrocytes. Furthermore, not every NG2 cell is fated to become an oligodendrocyte. Hence the term OPC can be fairly applied only when discussing the role of these cells in the oligodendrocyte lineage.展开更多
Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-r...Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.展开更多
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
The regulation of signal transmission speed is one of the most important capabilities of the biological nervous system.This study explores the mechanisms and methods for regulating signal transmission speed among nonm...The regulation of signal transmission speed is one of the most important capabilities of the biological nervous system.This study explores the mechanisms and methods for regulating signal transmission speed among nonmyelinated neurons within the same brain region,starting from spike-timing-dependent plasticity(STDP)of synapses.Building upon the Hodgkin-Huxley model,the dynamic behavior of synapses is incorporated,and the adaptive growth neuron(AGN)model is proposed.Artificial synaptic structures and neuronal physical nodes are also designed.The artificial synaptic structure exhibits unidirectionality,memory capacity,and STDP,enabling it to connect neuronal physical nodes through branching and merging structures.Furthermore,the artificial synapse can adjust signal transmission speed,regulate functional competition between different regions of the neuromorphic network,and promote information interaction.The findings of this study endow neuromorphic networks with the ability to regulate signal transmission speed over the long term,providing new insights into the development of neuromorphic networks.展开更多
Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at th...Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.展开更多
Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience...Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.展开更多
The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at syna...The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.展开更多
Microglia are the macrophages that populate the brain parenchyma.Research in the past decades has identified them as both essential guardians of the brain and significant contributors to various neurological diseases....Microglia are the macrophages that populate the brain parenchyma.Research in the past decades has identified them as both essential guardians of the brain and significant contributors to various neurological diseases.A highly versatile cell type,microglia have been shown to fulfill a multitude of critical roles in the central nervous system,including facilitating neurogenesis and myelination,pruning synapses,removing debris and waste,modulating neuronal activity,supporting the blood-brain barrier,repairing tissue damage,and surveilling against microbial invasions under physiological conditions(Prinz et al.,2021;Paolicelli et al.,2022).展开更多
The increasing complexity of intelligent sensing environments,driven by the growth of Internet of Things technologies,has created a strong demand for neuromorphic systems capable of real-time,low-power multisensory pe...The increasing complexity of intelligent sensing environments,driven by the growth of Internet of Things technologies,has created a strong demand for neuromorphic systems capable of real-time,low-power multisensory perception.Traditional sensory architectures,constrained by single-modal processing and centralized computing,struggle to meet the requirements of diverse and dynamic input conditions.Multisensory neuromorphic devices offer a promising solution by mimicking the distributed,event-driven processing of biological systems.Recent efforts have explored synaptic devices and material systems that respond to various input modalities,including visual,tactile,thermal,and chemical stimuli.However,challenges remain in signal conversion,encoding compatibility,and the fusion of heterogeneous inputs without loss of unisensory information.This review provides a comprehensive overview of the physical mechanisms,device behaviors,and integration strategies that underpin signal processing in neuromorphic hardware.We highlight synaptic mechanisms conducive to cross-modal interaction,analyze representative signal fusion approaches at the device level,and discuss future directions for constructing efficient,scalable,and biologically inspired multisensory neuromorphic systems.展开更多
The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have sugge...MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have suggested that miRNAs play important roles in regulating key aspects in the pathology of Alzheimer's disease,including the modulation and accumulation of amyloid-beta and tau proteins.Moreover,miRNAs have been implicated in the regulation of neuroinflammation thro ugh various inflammatory pathways,notably the nuclear factor kappa B signaling cascade.Additional emerging evidence has shown that miRNAs regulate synaptic growth and maturation,and they perform promising roles in regulating neuronal death and development.miRNAs also offer a novel avenue for direct reprogramming of neurons,representing a promising strategy for Alzheimer's disease treatment.The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology,influencing miRNA activity and disease progression.In this review,we comprehensively explore the role of different miRNAs in regulating various pathological processes associated with Alzheimer's disease,focusing primarily on four representative miRNAs:miR-9,miR-29,miR-126,and miR-146a for further exploration.We also discuss the influence of miRNA biogenesis on Alzheimer's disease,emphasizing how dysregulation of miRNA processing may contribute to the disease.Additionally,we highlight the potential of miRNAs as both diagnostic biomarke rs and therapeutic targets in Alzheimer's disease,along with promising vector delive ry strategies aimed at improving clinical outcomes.Finally,we discuss the challenges and limitations associated with the use of miRNAs in the diagnosis and treatment of Alzheimer's disease.By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents,we aim to provide insights that will inform future research and development in this promising field.展开更多
Alzheimer's disease(AD)is a serious disease associated with cognitive impairment,and synaptic loss and amyloid-beta(Aβ)deposition are closely related to its pathogenesis.D ocosahexaenoic acid(DHA)has been reporte...Alzheimer's disease(AD)is a serious disease associated with cognitive impairment,and synaptic loss and amyloid-beta(Aβ)deposition are closely related to its pathogenesis.D ocosahexaenoic acid(DHA)has been reported to alter the cognitive impairment associated with aging and reduce the risk of long-term development of AD.However,the effects of Aβon synapses and whether DHA has a protective effect on synapses remain unclear.In this study,APPSwe/PSEN1d E9 transgenic and wild type mice were used as experimental subjects to explore the effect of DHA on synaptic structure and function damaged by Aβ.Results showed that a large amount of Aβwas deposited in the brain of AD mice,and DHA intervention decreased the Aβdeposition(P<0.05).DHA decreased the apoptosis of nerve cells and the oxidative stress level induced by Aβ(P<0.01).Transmission electron microscopy results showed that DHA improved the synaptic structure and number,and the expression of synaptophysin was significantly upregulated by DHA(P<0.01).Besides,neurotransmitter release was regulated after DHA intervention,including the decreased Glu level and increasedγ-aminobutyric acid level,as well as the activity of ATPase was also increased by DHA.Importantly,the phosphorylation levels of tyrosine kinase B(Trk B),phospholipase C-gamma-1,calcium/calmodulin-dependent protein kinase II,extracellular regulated protein kinases(ERK1/2),and c AMP-response element binding protein(CREB)were upregulated by DHA(P<0.01).These data indicated that DHA could improve synaptic structure and function through the Trk B-Erk1/2-CREB pathway,thus playing a positive role in the pathological process of AD.展开更多
The rapid development of brain-like neural networks and secure data transmission technologies has placed greater demands on highly complex neural network systems and highly secure encryption methods.To this end,the pa...The rapid development of brain-like neural networks and secure data transmission technologies has placed greater demands on highly complex neural network systems and highly secure encryption methods.To this end,the paper proposes a novel high-dimensional memristor synapse-coupled hyperchaotic neural network by using the designed memristor as the synapse to connect an inertial neuron(IN)and a Hopfield neural network(HNN).By using numerical tools including bifurcation plots,phase plots,and basins of attraction,it is found that the dynamics of this system are closely related to the memristor coupling strength,self-connection synaptic weights,and inter-connection synaptic weights,and it can exhibit excellent hyperchaotic behaviors and coexisting multi-stable patterns.Through PSIM circuit simulations,the complex dynamics of the coupled IN-HNN system are verified.Furthermore,a DNA-encoded encryption algorithm is given,which utilizes generated hyperchaotic sequences to achieve encoding,operation,and decoding of DNA.The results show that this algorithm possesses strong robustness against statistical attacks,differential attacks,and noise interference,and can effectively resist known/selected plaintext attacks.This work will provide new ideas for the modeling of large-scale brainlike neural networks and high-security image encryption.展开更多
In recent years,optoelectronic synapses have garnered significant attention in the field of neuromorphic computing due to their integration of optical sensing and synaptic functions.In this work,we propose an optoelec...In recent years,optoelectronic synapses have garnered significant attention in the field of neuromorphic computing due to their integration of optical sensing and synaptic functions.In this work,we propose an optoelectronic synapse based on IGZO/Bi_(3.25)La_(0.75)Ti_(3)O_(12)heterojunction.Under UV light stimulation,this device can simulate a range of synaptic behaviors,including paired-pulse facilitation,spike-intensity-dependent plasticity,spike-number-dependent plasticity,spike-width-dependent plasticity,and the transition from short-term memory to long-term memory.The majority of perceptible information for humans is acquired through the visual system.The 3×3 retinal morphology synapse arrays constructed based on plasticity behaviors not only integrates light perception and storage functions but also exhibits adaptive adjustment capabilities to address image blurring caused by object movement.At the same time,in CNN recognition training,the device successfully simulates the learning-relearning mechanism of the human brain.These findings highlight the device's immense potential for applications in artificial vision systems.展开更多
Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and fu...Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and functionality of these cells in damaged brain regions remains challenging.Silk fibroin,a natural protein derived from silkworm silk,is a biocompatible material with exceptional properties that are useful for tissue engineering.Its biodegradability,mechanical robustness,and ability to promote cell growth make it particularly valuable for biomedical applications.Silk fibroin nanomaterials,which comprise silk fibroin processed into nanostructures,offer enhanced surface area,improved loading capacity for bioactive molecules,and superior nanoscale interactions with cells compared with bulk silk fibroin materials.In this study,we first extracted human-derived neural stem cells from a 14-week-old human fetus.Then,neural stem cells were loaded with 1%silk fibroin nanomaterials,which was identified as the optimal concentration to support human-derived neural stem cell growth and release of neurotrophic factors.Finally,1%silk fibroin nanomaterials were implanted into a rat model of hypoxic-ischemic brain injury.The results showed that,compared with the treatment with human-derived neural stem cells alone,silk fibroin hydrogel carrying human-derived neural stem cells was significantly more effective at alleviating brain tissue damage,increasing neurotrophic factor secretion in the brain microenvironment,and promoting motor and cognitive function recovery.These findings suggest that silk fibroin nanomaterials loaded with human-derived neural stem cells could be used to treat hypoxic-ischemic encephalopathy.However,the mechanisms and related signaling pathways by which hydrogels combined with cells exert their reparative effects still require further in-depth investigation.展开更多
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.展开更多
The traditional von Neumann architecture has demonstrated inefficiencies in parallel computing and adaptive learn-ing,rendering it incapable of meeting the growing demand for efficient and high-speed computing.Neuromo...The traditional von Neumann architecture has demonstrated inefficiencies in parallel computing and adaptive learn-ing,rendering it incapable of meeting the growing demand for efficient and high-speed computing.Neuromorphic comput-ing with significant advantages such as high parallelism and ultra-low power consumption is regarded as a promising pathway to overcome the limitations of conventional computers and achieve the next-generation artificial intelligence.Among various neuromorphic devices,the artificial synapses based on electrolyte-gated transistors stand out due to their low energy consump-tion,multimodal sensing/recording capabilities,and multifunctional integration.Moreover,the emerging optoelectronic neuro-morphic devices which combine the strengths of photonics and electronics have demonstrated substantial potential in the neu-romorphic computing field.Therefore,this article reviews recent advancements in electrolyte-gated optoelectronic neuromor-phic transistors.First,it provides an overview of artificial optoelectronic synapses and neurons,discussing aspects such as device structures,operating mechanisms,and neuromorphic functionalities.Next,the potential applications of optoelectronic synapses in different areas such as artificial visual system,pain system,and tactile perception systems are elaborated.Finally,the current challenges are summarized,and future directions for their developments are proposed.展开更多
The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to d...The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to develop artificial visual synapses that integrate optical sensing and synaptic functions.This study fully leverages the excellent photoresponsivity proper-ties of the PM6:Y6 system to construct a vertical photo-tunable organic memristor and conducts in-depth research on its resis-tive switching performance,photodetection capability,and simulation of photo-synaptic behavior,showcasing its excellent per-formance in processing visual information and simulating neuromorphic behaviors.The device achieves stable and gradual resis-tance change,successfully simulating voltage-controlled long-term potentiation/depression(LTP/LTD),and exhibits various photo-electric synergistic regulation of synaptic plasticity.Moreover,the device has successfully simulated the image percep-tion and recognition functions of the human visual nervous system.The non-volatile Au/PM6:Y6/ITO memristor is used as an artificial synapse and neuron modeling,building a hierarchical coordinated processing SLP-CNN cascade neural network for visual image recognition training,its linear tunable photoconductivity characteristic serves as the weight update of the net-work,achieving a recognition accuracy of up to 93.4%.Compared with the single-layer visual target recognition model,this scheme has improved the recognition accuracy by 19.2%.展开更多
Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse functi...Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.展开更多
基金supported by NIH NS079631,Shriners Hospitals for Children and Craig H.Neilsen Foundation
文摘Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes that myelinate central nervous system （CNS） axons. Evidence suggests, however, that they have other functions, besides differentiating into oligodendrocytes. Most notably, the OPCs/NG2 cells are uni- formly distributed in grey matter as well as in white matter, which matches poorly with the distribution of myelinating oligodendrocytes. Furthermore, not every NG2 cell is fated to become an oligodendrocyte. Hence the term OPC can be fairly applied only when discussing the role of these cells in the oligodendrocyte lineage.
基金supported by the National Natural Science Foundation of China(No.82401445 and 82271249)the China Postdoctoral Science Foundation(No.2024M752251)+3 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20241141)the Sichuan Science and Technology Program(No.2024NSFSC1636 and 2025ZNSFSC1645)the Postdoctoral Research Fund of West China Hospital of Sichuan University(No.2024HXBH013)1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(No.ZYYC23002)。
文摘Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by the National Natural Science Foundation of China(Grant No.62171182)the Natural Scienceof Hunan Province(Grant No.2025JJ50345)the Postgraduate Scientific Research Innovation Project of Hunan Province(Grant No.CX20240452)。
文摘The regulation of signal transmission speed is one of the most important capabilities of the biological nervous system.This study explores the mechanisms and methods for regulating signal transmission speed among nonmyelinated neurons within the same brain region,starting from spike-timing-dependent plasticity(STDP)of synapses.Building upon the Hodgkin-Huxley model,the dynamic behavior of synapses is incorporated,and the adaptive growth neuron(AGN)model is proposed.Artificial synaptic structures and neuronal physical nodes are also designed.The artificial synaptic structure exhibits unidirectionality,memory capacity,and STDP,enabling it to connect neuronal physical nodes through branching and merging structures.Furthermore,the artificial synapse can adjust signal transmission speed,regulate functional competition between different regions of the neuromorphic network,and promote information interaction.The findings of this study endow neuromorphic networks with the ability to regulate signal transmission speed over the long term,providing new insights into the development of neuromorphic networks.
基金supported by Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province,No.20210302123486(to WJ).
文摘Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.
基金supported by the National Natural Science Foundation of China,No.31760290,82160688the Key Development Areas Project of Ganzhou Science and Technology,No.2022B-SF9554(all to XL)。
文摘Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.
基金supported by grants from the National Key R&D Program of China(2021YFA1101300,2021YFA1101800,2020YFA0112503,and 2024YFC2511103)the National Natural Science Foundation of China(82330033,82030029,82401375,81970882,92149304,and 81970883)+7 种基金the Natural Science Foundation of Jiangsu Province(BK20232007)the Science and Technology Department of Sichuan Province(2021YFS0371)Shenzhen Fundamental Research Program(JCYJ20210324125608022)the Open Project Fund of Guangdong Academy of Medical Sciences(YKY-KF202201)Beijing Natural Science Foundation(Z200019)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the China Postdoctoral Science Foundation(2023TQ0056,2023M730575,and GZC20230435)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB822).
文摘The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.
基金funded by NIH grants HL154720-03S1, AG057587, AG074283, DK122708-03S1, BrightFocus ADR A20183775Brown Foundation 2020 Healthy Aging Initiative (to WC)
文摘Microglia are the macrophages that populate the brain parenchyma.Research in the past decades has identified them as both essential guardians of the brain and significant contributors to various neurological diseases.A highly versatile cell type,microglia have been shown to fulfill a multitude of critical roles in the central nervous system,including facilitating neurogenesis and myelination,pruning synapses,removing debris and waste,modulating neuronal activity,supporting the blood-brain barrier,repairing tissue damage,and surveilling against microbial invasions under physiological conditions(Prinz et al.,2021;Paolicelli et al.,2022).
基金the financial support from the National Key Research and Development Program of China(Grant No.2022YFB4400100)the NSFC under Grant Nos.92477102 and 62122084the open research fund of Songshan Lake Materials Laboratory 2023SLABFK09。
文摘The increasing complexity of intelligent sensing environments,driven by the growth of Internet of Things technologies,has created a strong demand for neuromorphic systems capable of real-time,low-power multisensory perception.Traditional sensory architectures,constrained by single-modal processing and centralized computing,struggle to meet the requirements of diverse and dynamic input conditions.Multisensory neuromorphic devices offer a promising solution by mimicking the distributed,event-driven processing of biological systems.Recent efforts have explored synaptic devices and material systems that respond to various input modalities,including visual,tactile,thermal,and chemical stimuli.However,challenges remain in signal conversion,encoding compatibility,and the fusion of heterogeneous inputs without loss of unisensory information.This review provides a comprehensive overview of the physical mechanisms,device behaviors,and integration strategies that underpin signal processing in neuromorphic hardware.We highlight synaptic mechanisms conducive to cross-modal interaction,analyze representative signal fusion approaches at the device level,and discuss future directions for constructing efficient,scalable,and biologically inspired multisensory neuromorphic systems.
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
基金National Natural Science Foundation of China,No.82405067(to YW)。
文摘MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have suggested that miRNAs play important roles in regulating key aspects in the pathology of Alzheimer's disease,including the modulation and accumulation of amyloid-beta and tau proteins.Moreover,miRNAs have been implicated in the regulation of neuroinflammation thro ugh various inflammatory pathways,notably the nuclear factor kappa B signaling cascade.Additional emerging evidence has shown that miRNAs regulate synaptic growth and maturation,and they perform promising roles in regulating neuronal death and development.miRNAs also offer a novel avenue for direct reprogramming of neurons,representing a promising strategy for Alzheimer's disease treatment.The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology,influencing miRNA activity and disease progression.In this review,we comprehensively explore the role of different miRNAs in regulating various pathological processes associated with Alzheimer's disease,focusing primarily on four representative miRNAs:miR-9,miR-29,miR-126,and miR-146a for further exploration.We also discuss the influence of miRNA biogenesis on Alzheimer's disease,emphasizing how dysregulation of miRNA processing may contribute to the disease.Additionally,we highlight the potential of miRNAs as both diagnostic biomarke rs and therapeutic targets in Alzheimer's disease,along with promising vector delive ry strategies aimed at improving clinical outcomes.Finally,we discuss the challenges and limitations associated with the use of miRNAs in the diagnosis and treatment of Alzheimer's disease.By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents,we aim to provide insights that will inform future research and development in this promising field.
基金supported by Natural Science Foundation of Henan Province of China(242300421536)College Students’Innovation and Entrepreneurship Training Program of Xinxiang Medicine University(202410472024).
文摘Alzheimer's disease(AD)is a serious disease associated with cognitive impairment,and synaptic loss and amyloid-beta(Aβ)deposition are closely related to its pathogenesis.D ocosahexaenoic acid(DHA)has been reported to alter the cognitive impairment associated with aging and reduce the risk of long-term development of AD.However,the effects of Aβon synapses and whether DHA has a protective effect on synapses remain unclear.In this study,APPSwe/PSEN1d E9 transgenic and wild type mice were used as experimental subjects to explore the effect of DHA on synaptic structure and function damaged by Aβ.Results showed that a large amount of Aβwas deposited in the brain of AD mice,and DHA intervention decreased the Aβdeposition(P<0.05).DHA decreased the apoptosis of nerve cells and the oxidative stress level induced by Aβ(P<0.01).Transmission electron microscopy results showed that DHA improved the synaptic structure and number,and the expression of synaptophysin was significantly upregulated by DHA(P<0.01).Besides,neurotransmitter release was regulated after DHA intervention,including the decreased Glu level and increasedγ-aminobutyric acid level,as well as the activity of ATPase was also increased by DHA.Importantly,the phosphorylation levels of tyrosine kinase B(Trk B),phospholipase C-gamma-1,calcium/calmodulin-dependent protein kinase II,extracellular regulated protein kinases(ERK1/2),and c AMP-response element binding protein(CREB)were upregulated by DHA(P<0.01).These data indicated that DHA could improve synaptic structure and function through the Trk B-Erk1/2-CREB pathway,thus playing a positive role in the pathological process of AD.
基金Project supported by the Training Plan of Young Backbone Teachers in Universities of Henan Province(Grant No.2023GGJS142)the Key Scientific Research of Colleges and Universities in Henan Province,China(Grant No.25A120009)+1 种基金Changzhou Leading Innovative Talent Introduction and Cultivation Project(Grant No.CQ20240102)Changzhou Applied Basic Research Program(Grant No.CJ20253065)。
文摘The rapid development of brain-like neural networks and secure data transmission technologies has placed greater demands on highly complex neural network systems and highly secure encryption methods.To this end,the paper proposes a novel high-dimensional memristor synapse-coupled hyperchaotic neural network by using the designed memristor as the synapse to connect an inertial neuron(IN)and a Hopfield neural network(HNN).By using numerical tools including bifurcation plots,phase plots,and basins of attraction,it is found that the dynamics of this system are closely related to the memristor coupling strength,self-connection synaptic weights,and inter-connection synaptic weights,and it can exhibit excellent hyperchaotic behaviors and coexisting multi-stable patterns.Through PSIM circuit simulations,the complex dynamics of the coupled IN-HNN system are verified.Furthermore,a DNA-encoded encryption algorithm is given,which utilizes generated hyperchaotic sequences to achieve encoding,operation,and decoding of DNA.The results show that this algorithm possesses strong robustness against statistical attacks,differential attacks,and noise interference,and can effectively resist known/selected plaintext attacks.This work will provide new ideas for the modeling of large-scale brainlike neural networks and high-security image encryption.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.11574057 and12172093)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2021A1515012607)。
文摘In recent years,optoelectronic synapses have garnered significant attention in the field of neuromorphic computing due to their integration of optical sensing and synaptic functions.In this work,we propose an optoelectronic synapse based on IGZO/Bi_(3.25)La_(0.75)Ti_(3)O_(12)heterojunction.Under UV light stimulation,this device can simulate a range of synaptic behaviors,including paired-pulse facilitation,spike-intensity-dependent plasticity,spike-number-dependent plasticity,spike-width-dependent plasticity,and the transition from short-term memory to long-term memory.The majority of perceptible information for humans is acquired through the visual system.The 3×3 retinal morphology synapse arrays constructed based on plasticity behaviors not only integrates light perception and storage functions but also exhibits adaptive adjustment capabilities to address image blurring caused by object movement.At the same time,in CNN recognition training,the device successfully simulates the learning-relearning mechanism of the human brain.These findings highlight the device's immense potential for applications in artificial vision systems.
基金Dalian Science and Technology Talent Innovation Support Policy Implementation Plan High-Level Talent Team,No.2022RG18(to JL)the Science and Technology Plan Orientation of Liaoning Province,No.[2021]49(to JL)+1 种基金Dalian High-Level Talent Innovation Support Plan,No.2021RQ028(to CH)Natural Science Foundation of Liaoning Province,No.2022-BS-238(to CH).
文摘Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and functionality of these cells in damaged brain regions remains challenging.Silk fibroin,a natural protein derived from silkworm silk,is a biocompatible material with exceptional properties that are useful for tissue engineering.Its biodegradability,mechanical robustness,and ability to promote cell growth make it particularly valuable for biomedical applications.Silk fibroin nanomaterials,which comprise silk fibroin processed into nanostructures,offer enhanced surface area,improved loading capacity for bioactive molecules,and superior nanoscale interactions with cells compared with bulk silk fibroin materials.In this study,we first extracted human-derived neural stem cells from a 14-week-old human fetus.Then,neural stem cells were loaded with 1%silk fibroin nanomaterials,which was identified as the optimal concentration to support human-derived neural stem cell growth and release of neurotrophic factors.Finally,1%silk fibroin nanomaterials were implanted into a rat model of hypoxic-ischemic brain injury.The results showed that,compared with the treatment with human-derived neural stem cells alone,silk fibroin hydrogel carrying human-derived neural stem cells was significantly more effective at alleviating brain tissue damage,increasing neurotrophic factor secretion in the brain microenvironment,and promoting motor and cognitive function recovery.These findings suggest that silk fibroin nanomaterials loaded with human-derived neural stem cells could be used to treat hypoxic-ischemic encephalopathy.However,the mechanisms and related signaling pathways by which hydrogels combined with cells exert their reparative effects still require further in-depth investigation.
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.
基金supported by the Hunan Science Fund for Distinguished Young Scholars(2023JJ10069)the National Natural Science Foundation of China(52172169)the Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performance,Central South University(ZZYJKT2024-02).
文摘The traditional von Neumann architecture has demonstrated inefficiencies in parallel computing and adaptive learn-ing,rendering it incapable of meeting the growing demand for efficient and high-speed computing.Neuromorphic comput-ing with significant advantages such as high parallelism and ultra-low power consumption is regarded as a promising pathway to overcome the limitations of conventional computers and achieve the next-generation artificial intelligence.Among various neuromorphic devices,the artificial synapses based on electrolyte-gated transistors stand out due to their low energy consump-tion,multimodal sensing/recording capabilities,and multifunctional integration.Moreover,the emerging optoelectronic neuro-morphic devices which combine the strengths of photonics and electronics have demonstrated substantial potential in the neu-romorphic computing field.Therefore,this article reviews recent advancements in electrolyte-gated optoelectronic neuromor-phic transistors.First,it provides an overview of artificial optoelectronic synapses and neurons,discussing aspects such as device structures,operating mechanisms,and neuromorphic functionalities.Next,the potential applications of optoelectronic synapses in different areas such as artificial visual system,pain system,and tactile perception systems are elaborated.Finally,the current challenges are summarized,and future directions for their developments are proposed.
基金the National Natural Science Foundation of China(62111540271)Natural Science Foundation of Anhui Province(2308085MF207).
文摘The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to develop artificial visual synapses that integrate optical sensing and synaptic functions.This study fully leverages the excellent photoresponsivity proper-ties of the PM6:Y6 system to construct a vertical photo-tunable organic memristor and conducts in-depth research on its resis-tive switching performance,photodetection capability,and simulation of photo-synaptic behavior,showcasing its excellent per-formance in processing visual information and simulating neuromorphic behaviors.The device achieves stable and gradual resis-tance change,successfully simulating voltage-controlled long-term potentiation/depression(LTP/LTD),and exhibits various photo-electric synergistic regulation of synaptic plasticity.Moreover,the device has successfully simulated the image percep-tion and recognition functions of the human visual nervous system.The non-volatile Au/PM6:Y6/ITO memristor is used as an artificial synapse and neuron modeling,building a hierarchical coordinated processing SLP-CNN cascade neural network for visual image recognition training,its linear tunable photoconductivity characteristic serves as the weight update of the net-work,achieving a recognition accuracy of up to 93.4%.Compared with the single-layer visual target recognition model,this scheme has improved the recognition accuracy by 19.2%.
基金supported by NIH/NIMH grant R01MH111619(to SQ),R21AG078700(to SQ)Institute of Mental Health Research(IMHR,Level 1 funding,to SQ and DF)institution startup fund from The University of Arizona(to SQ)。
文摘Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.
