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
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by...Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by which the need for sleep accumulates during wakefulness and dissipates during sleep-remain incompletely understood.This article explores the latest advancements in sleep research,focusing on the role of synaptic plasticity in sleep homeostasis,as illuminated by Sawada et al.(2024).展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy s...Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.展开更多
Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting th...Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.展开更多
Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neur...Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
In recent years,research focusing on synaptic device based on phototransistors has provided a new method for asso-ciative learning and neuromorphic computing.A TiO_(2)/AlGaN/GaN heterostructure-based synaptic phototra...In recent years,research focusing on synaptic device based on phototransistors has provided a new method for asso-ciative learning and neuromorphic computing.A TiO_(2)/AlGaN/GaN heterostructure-based synaptic phototransistor is fabricated and measured,integrating a TiO_(2)nanolayer gate and a two-dimensional electron gas(2DEG)channel to mimic the synaptic weight and the synaptic cleft,respectively.The maximum drain to source current is 10 nA,while the device is driven at a reverse bias not exceeding-2.5 V.A excitatory postsynaptic current(EPSC)of 200 nA can be triggered by a 365 nm UVA light spike with the duration of 1 s at light intensity of 1.35μW·cm^(-2).Multiple synaptic neuromorphic functions,including EPSC,short-term/long-term plasticity(STP/LTP)and paried-pulse facilitation(PPF),are effectively mimicked by our GaN-based het-erostructure synaptic device.In the typical Pavlov’s dog experiment,we demonstrate that the device can achieve"retraining"process to extend memory time through enhancing the intensity of synaptic weight,which is similar to the working mecha-nism of human brain.展开更多
As the demand for advanced computational systems capable of handling large data volumes rises,nano-electronic devices,such as memristors,are being developed for efficient data processing,especially in reservoir comput...As the demand for advanced computational systems capable of handling large data volumes rises,nano-electronic devices,such as memristors,are being developed for efficient data processing,especially in reservoir computing(RC).RC enables the processing of temporal information with minimal training costs,making it a promising approach for neuromorphic computing.However,current memristor devices of-ten suffer from limitations in dynamic conductance and temporal behavior,which affects their perfor-mance in these applications.In this study,we present a multilayered indium-tin-oxide(ITO)/ZnO/indium-gallium-zinc oxide(IGZO)/ZnO/ITO memristor fabricated via radiofrequency sputtering to explore its fil-amentary and nonfilamentary resistive switching(RS)characteristics.High-resolution transmission elec-tron microscopy confirmed the polycrystalline structure of the ZnO/IGZO/ZnO active layer.Dual-switching modes were demonstrated by controlling the current compliance(I_(CC)).In the filamentary mode,the memristor exhibited a large memory window(10^(3)),low-operating voltages(±2 V),excellent cycle-to-cycle stability,and multilevel switching with controlled reset-stop voltages,making it suitable for high-density memory applications.Nonfilamentary switching demonstrated stable on/off ratios above 10,en-durance up to 102 cycles,and retention suited for short-term memory.Key synaptic behaviors,such as paired-pulse facilitation(PPF),post-tetanic potentiation(PTP),and spike-rate dependent plasticity(SRDP)were successfully emulated by modulating pulse amplitude,width,and interval.Experience-dependent plasticity(EDP)was also demonstrated,further replicating biological synaptic functions.These tempo-ral properties were utilized to develop a 4-bit reservoir computing system with 16 distinct conductance states,enabling efficient information encoding.For image recognition tasks,convolutional neural net-work(CNN)simulations achieved a high accuracy of 98.45%after 25 training epochs,outperforming the accuracy achieved following artificial neural network(ANN)simulations(87.79%).These findings demon-strate that the multilayered memristor exhibits high performance in neuromorphic systems,particularly for complex pattern recognition tasks,such as digit and letter classification.展开更多
To address the increasing demand for massive data storage and processing,brain-inspired neuromorphic comput-ing systems based on artificial synaptic devices have been actively developed in recent years.Among the vario...To address the increasing demand for massive data storage and processing,brain-inspired neuromorphic comput-ing systems based on artificial synaptic devices have been actively developed in recent years.Among the various materials inves-tigated for the fabrication of synaptic devices,silicon carbide(SiC)has emerged as a preferred choices due to its high electron mobility,superior thermal conductivity,and excellent thermal stability,which exhibits promising potential for neuromorphic applications in harsh environments.In this review,the recent progress in SiC-based synaptic devices is summarized.Firstly,an in-depth discussion is conducted regarding the categories,working mechanisms,and structural designs of these devices.Subse-quently,several application scenarios for SiC-based synaptic devices are presented.Finally,a few perspectives and directions for their future development are outlined.展开更多
In this data explosion era,ensuring the secure storage,access,and transmission of information is imperative,encom-passing all aspects ranging from safeguarding personal devices to formulating national information secu...In this data explosion era,ensuring the secure storage,access,and transmission of information is imperative,encom-passing all aspects ranging from safeguarding personal devices to formulating national information security strategies.Leverag-ing the potential offered by dual-type carriers for transportation and employing optical modulation techniques to develop high reconfigurable ambipolar optoelectronic transistors enables effective implementation of information destruction after read-ing,thereby guaranteeing data security.In this study,a reconfigurable ambipolar optoelectronic synaptic transistor based on poly(3-hexylthiophene)(P3HT)and poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)](N2200)blend film was fabricated through solution-processed method.The resulting transistor exhib-ited a relatively large ON/OFF ratio of 10^(3) in both n-and p-type regions,and tunable photoconductivity after light illumination,particularly with green light.The photo-generated carriers could be effectively trapped under the gate bias,indicating its poten-tial application in mimicking synaptic behaviors.Furthermore,the synaptic plasticity,including volatile/non-volatile and excita-tory/inhibitory characteristics,could be finely modulated by electrical and optical stimuli.These optoelectronic reconfigurable properties enable the realization of information light assisted burn after reading.This study not only offers valuable insights for the advancement of high-performance ambipolar organic optoelectronic synaptic transistors but also presents innovative ideas for the future information security access systems.展开更多
The rapid growth of artificial intelligence has accelerated data generation,which increasingly exposes the limitations faced by traditional computational architectures,particularly in terms of energy consumption and d...The rapid growth of artificial intelligence has accelerated data generation,which increasingly exposes the limitations faced by traditional computational architectures,particularly in terms of energy consumption and data latency.In contrast,data-centric computing that integrates processing and storage has the potential of reducing latency and energy usage.Organic optoelectronic synaptic transistors have emerged as one type of promising devices to implement the data-centric com-puting paradigm owing to their superiority of flexibility,low cost,and large-area fabrication.However,sophisticated functions including vector-matrix multiplication that a single device can achieve are limited.Thus,the fabrication and utilization of organic optoelectronic synaptic transistor arrays(OOSTAs)are imperative.Here,we summarize the recent advances in OOSTAs.Various strategies for manufacturing OOSTAs are introduced,including coating and casting,physical vapor deposition,printing,and photolithography.Furthermore,innovative applications of the OOSTA system integration are discussed,including neuromor-phic visual systems and neuromorphic computing systems.At last,challenges and future perspectives of utilizing OOSTAs in real-world applications are discussed.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal...Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.展开更多
The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanism...The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanisms have not been comprehensively investigated.Previous studies have focused extensively on its neuromodulatory effects and have also identified multiple exercise-associated molecular substrates and blood-borne metabolites,including neurotrophic factors,monoamine neurotransmitters,neuroinflammatory cytokines,kynurenine,N-lactoylphenylalanine,and the ketone bodyβ-hydroxybutyrate[2].Notably,lactate,a common energy source derived from cellular glycolysis in response to intensive exercise,has recently been reported to exert antidepressant activity[3].However,a detailed mechanistic explanation is lacking.展开更多
Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the targe...Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the target of PD therapy.However,the identification of effective anti-ferroptosis treatments remains elusive.This study explores the therapeutic potential of low-intensity ultrasound(US)in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD.We demonstrate that optimized US stimulation(610 kHz,0.2 W/cm2)activates Piezo1 channel-mediated fast endophilin-mediated endocytosis,which promotes SV recycling and synaptic function,presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents.Repaired SV recycling in turn reduces the accumulation ofα-syn expression and ferroptotic cell death.These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.展开更多
Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-sp...Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-specific peptidase 47(USP47)influences synaptic plasticity and its link to epilepsy.We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines.Furthermore,USP47 inhibited the degradation of the ubiquitinatedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)subunit glutamate receptor 1(GluR1),which is associated with synaptic plasticity.In addition,elevated levels of USP47 were found in epileptic mice,and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures.To summarize,we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation.Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.展开更多
Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related ps...Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes.However,its precise role and mechanism of action in stress susceptibility remain elusive.In this study,we found a significant reduction in GADD45B expression specifically in the ventral,but not the dorsal hippocampal CA1(dCA1)of stress-susceptible mice.Furthermore,we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation(LTP)in the ventral hippocampal CA1(vCA1).Importantly,through pharmacological inhibition using the NMDA receptor antagonist MK801,we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP.Collectively,these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.展开更多
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 Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by Japan Society forthe Promotion of Science(JSPS)Grants-in-Aidfor Scientific Research(KAKENHI)(20H05894,20H05903,21K15136,22K21351,23H02518A,23H02663,and 23K18147 to SS),JST-CREST(JPMJCR24T4 to SS),the World PremierInternational Research Center Initiative(WPI)fromthe Ministry of Education,Culture,Sports,Scienceand Technology(MEXT)to SS(WPI-IIIS),the TopRunners in Strategy of Transborder AdvancedResearches(TRiSTAR)by the MEXT to SSJapanAgency for Medical Research and Development(AMED)(JP21zf0127005 to SS),Cell ScienceResearch Foundation Grant to YI,38th Brain ScienceFoundation Research Grant to YI,Research Granton Biogenic Amines and Neurological Diseases(Sumitomo pharma)to YI.
文摘Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by which the need for sleep accumulates during wakefulness and dissipates during sleep-remain incompletely understood.This article explores the latest advancements in sleep research,focusing on the role of synaptic plasticity in sleep homeostasis,as illuminated by Sawada et al.(2024).
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
基金supported by the National Natural Science Foundation of China,Nos.81701040(to HM),82071180(to HM),82271206(to TL),82171191(to YW),82371211(to YW)the Natural Science Foundation of Beijing,No.7212023(to HM)Key Subject of the Natural Science Foundation ofJiangsu Province for Colleges and Universities,No.23KJA320009(to YW).
文摘Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.
基金supported by the National Natural Science Foundation of China,Nos.81772453(to DX),81974358(to DX),81973157(to JZ),82173646(to JZ),82302866(to YZ)。
文摘Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord injury.Neuromagnetic stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor cortex.However,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains unclear.In this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 vertebra.We then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 post-injury.At day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of rats.Additionally,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal cord.Furthermore,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin II.Taken together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory responses.These findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.
基金supported by the Hefei Comprehensive National Science Center Hefei Brain Project(to KW)the National Natural Science Foundation of China,Nos.31970979(to KW),82101498(to XW)the STI2030-Major Projects,No.2021ZD0201800(to PH).
文摘Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by the National Key R&D Program of China(2021YFB3601000,2021YFB3601004)the National Key R&D Program of China(2022YFB3604702)the Chinese Academy of Sciences.
文摘In recent years,research focusing on synaptic device based on phototransistors has provided a new method for asso-ciative learning and neuromorphic computing.A TiO_(2)/AlGaN/GaN heterostructure-based synaptic phototransistor is fabricated and measured,integrating a TiO_(2)nanolayer gate and a two-dimensional electron gas(2DEG)channel to mimic the synaptic weight and the synaptic cleft,respectively.The maximum drain to source current is 10 nA,while the device is driven at a reverse bias not exceeding-2.5 V.A excitatory postsynaptic current(EPSC)of 200 nA can be triggered by a 365 nm UVA light spike with the duration of 1 s at light intensity of 1.35μW·cm^(-2).Multiple synaptic neuromorphic functions,including EPSC,short-term/long-term plasticity(STP/LTP)and paried-pulse facilitation(PPF),are effectively mimicked by our GaN-based het-erostructure synaptic device.In the typical Pavlov’s dog experiment,we demonstrate that the device can achieve"retraining"process to extend memory time through enhancing the intensity of synaptic weight,which is similar to the working mecha-nism of human brain.
基金supported by the National R&D Pro-gram through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(Nos.RS-2024-00356939 and RS-2024-00405691).
文摘As the demand for advanced computational systems capable of handling large data volumes rises,nano-electronic devices,such as memristors,are being developed for efficient data processing,especially in reservoir computing(RC).RC enables the processing of temporal information with minimal training costs,making it a promising approach for neuromorphic computing.However,current memristor devices of-ten suffer from limitations in dynamic conductance and temporal behavior,which affects their perfor-mance in these applications.In this study,we present a multilayered indium-tin-oxide(ITO)/ZnO/indium-gallium-zinc oxide(IGZO)/ZnO/ITO memristor fabricated via radiofrequency sputtering to explore its fil-amentary and nonfilamentary resistive switching(RS)characteristics.High-resolution transmission elec-tron microscopy confirmed the polycrystalline structure of the ZnO/IGZO/ZnO active layer.Dual-switching modes were demonstrated by controlling the current compliance(I_(CC)).In the filamentary mode,the memristor exhibited a large memory window(10^(3)),low-operating voltages(±2 V),excellent cycle-to-cycle stability,and multilevel switching with controlled reset-stop voltages,making it suitable for high-density memory applications.Nonfilamentary switching demonstrated stable on/off ratios above 10,en-durance up to 102 cycles,and retention suited for short-term memory.Key synaptic behaviors,such as paired-pulse facilitation(PPF),post-tetanic potentiation(PTP),and spike-rate dependent plasticity(SRDP)were successfully emulated by modulating pulse amplitude,width,and interval.Experience-dependent plasticity(EDP)was also demonstrated,further replicating biological synaptic functions.These tempo-ral properties were utilized to develop a 4-bit reservoir computing system with 16 distinct conductance states,enabling efficient information encoding.For image recognition tasks,convolutional neural net-work(CNN)simulations achieved a high accuracy of 98.45%after 25 training epochs,outperforming the accuracy achieved following artificial neural network(ANN)simulations(87.79%).These findings demon-strate that the multilayered memristor exhibits high performance in neuromorphic systems,particularly for complex pattern recognition tasks,such as digit and letter classification.
基金supported by the Natural Science Foundation of Zhejiang Province(Grant No.LQ24F040007)the National Natural Science Foundation of China(Grant No.U22A2075)the Opening Project of State Key Laboratory of Polymer Materials Engineering(Sichuan University)(Grant No.sklpme2024-1-21).
文摘To address the increasing demand for massive data storage and processing,brain-inspired neuromorphic comput-ing systems based on artificial synaptic devices have been actively developed in recent years.Among the various materials inves-tigated for the fabrication of synaptic devices,silicon carbide(SiC)has emerged as a preferred choices due to its high electron mobility,superior thermal conductivity,and excellent thermal stability,which exhibits promising potential for neuromorphic applications in harsh environments.In this review,the recent progress in SiC-based synaptic devices is summarized.Firstly,an in-depth discussion is conducted regarding the categories,working mechanisms,and structural designs of these devices.Subse-quently,several application scenarios for SiC-based synaptic devices are presented.Finally,a few perspectives and directions for their future development are outlined.
基金the National Natural-Science Foundation of China(Grant No.62304137)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515012479,2024A1515011737,and 2024A1515010006)+4 种基金the Science and Technology Innovation Commission of Shenzhen(Grant No.JCYJ20220818100206013)RSC Researcher Collaborations Grant(Grant No.C23-2422436283)State Key Laboratory of Radio Frequency Heterogeneous Integration(Independent Scientific Research Program No.2024010)the Project on Frontier and Interdisciplinary Research Assessment,Academic Divisions of the Chinese Academy of Sciences(Grant No.XK2023XXA002)NTUT-SZU Joint Research Program.
文摘In this data explosion era,ensuring the secure storage,access,and transmission of information is imperative,encom-passing all aspects ranging from safeguarding personal devices to formulating national information security strategies.Leverag-ing the potential offered by dual-type carriers for transportation and employing optical modulation techniques to develop high reconfigurable ambipolar optoelectronic transistors enables effective implementation of information destruction after read-ing,thereby guaranteeing data security.In this study,a reconfigurable ambipolar optoelectronic synaptic transistor based on poly(3-hexylthiophene)(P3HT)and poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)](N2200)blend film was fabricated through solution-processed method.The resulting transistor exhib-ited a relatively large ON/OFF ratio of 10^(3) in both n-and p-type regions,and tunable photoconductivity after light illumination,particularly with green light.The photo-generated carriers could be effectively trapped under the gate bias,indicating its poten-tial application in mimicking synaptic behaviors.Furthermore,the synaptic plasticity,including volatile/non-volatile and excita-tory/inhibitory characteristics,could be finely modulated by electrical and optical stimuli.These optoelectronic reconfigurable properties enable the realization of information light assisted burn after reading.This study not only offers valuable insights for the advancement of high-performance ambipolar organic optoelectronic synaptic transistors but also presents innovative ideas for the future information security access systems.
基金supported by the National Key Research and Development Program of China(2021YFA1101303)the National Natural Science Foundation of China(62374115)the Innovation Program of Shanghai Municipal Education Commission(2021-01-07-00-07-E00096).
文摘The rapid growth of artificial intelligence has accelerated data generation,which increasingly exposes the limitations faced by traditional computational architectures,particularly in terms of energy consumption and data latency.In contrast,data-centric computing that integrates processing and storage has the potential of reducing latency and energy usage.Organic optoelectronic synaptic transistors have emerged as one type of promising devices to implement the data-centric com-puting paradigm owing to their superiority of flexibility,low cost,and large-area fabrication.However,sophisticated functions including vector-matrix multiplication that a single device can achieve are limited.Thus,the fabrication and utilization of organic optoelectronic synaptic transistor arrays(OOSTAs)are imperative.Here,we summarize the recent advances in OOSTAs.Various strategies for manufacturing OOSTAs are introduced,including coating and casting,physical vapor deposition,printing,and photolithography.Furthermore,innovative applications of the OOSTA system integration are discussed,including neuromor-phic visual systems and neuromorphic computing systems.At last,challenges and future perspectives of utilizing OOSTAs in real-world applications are discussed.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金supported by grants from the National Natural Science Foundation of China(31970957 and 31471078)the Shanghai Science and Technology Commission(19ZR1416600)a 2021-JCJQ-JJ-1089 fund.
文摘Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
基金supported by grants from the National Natural Science Foundation of China(32271062 and 82305117)Science and Technology Program of Guangzhou,China(2023A04J0458)+1 种基金Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases(2023KT15524)the China Postdoctoral Science Foundation(2024M751343).
文摘The health benefits of physical exercise are well established and have been observed in both human studies and rodent models[1],improving overall health and stress resilience.However,the underlying molecular mechanisms have not been comprehensively investigated.Previous studies have focused extensively on its neuromodulatory effects and have also identified multiple exercise-associated molecular substrates and blood-borne metabolites,including neurotrophic factors,monoamine neurotransmitters,neuroinflammatory cytokines,kynurenine,N-lactoylphenylalanine,and the ketone bodyβ-hydroxybutyrate[2].Notably,lactate,a common energy source derived from cellular glycolysis in response to intensive exercise,has recently been reported to exert antidepressant activity[3].However,a detailed mechanistic explanation is lacking.
基金supported by the National Science Found for Young Scientists of China(82101339 and 22206051)the General Program of Natural Science Fund of Jiangsu Province(BK20221205)the General Program of Natural Science Research of Jiangsu Higher Education Institutions of China(20 KJB320034).
文摘Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the target of PD therapy.However,the identification of effective anti-ferroptosis treatments remains elusive.This study explores the therapeutic potential of low-intensity ultrasound(US)in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD.We demonstrate that optimized US stimulation(610 kHz,0.2 W/cm2)activates Piezo1 channel-mediated fast endophilin-mediated endocytosis,which promotes SV recycling and synaptic function,presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents.Repaired SV recycling in turn reduces the accumulation ofα-syn expression and ferroptotic cell death.These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.
基金supported by grants from the National Natural Science Foundation of China(82071458 and 32160190)the United Foundation of Zunyi Municipality(Zunshikehe HZ Zi(2021)14)+3 种基金the Science and Technology Project of Guizhou Provincial Health Commission(gzwkj2021-020)the Guizhou Epilepsy Basic and Clinical Research Scientific,Technological Innovation Talent Team Project(CXTD[2022]013)the Excellent Young Talents Training Program of the Affiliated Hospital of Zunyi Medical University(rc220220906)the Guizhou Provincial Hundred Level Innovative Talents Funds(GCC-2022-038-1).
文摘Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-specific peptidase 47(USP47)influences synaptic plasticity and its link to epilepsy.We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines.Furthermore,USP47 inhibited the degradation of the ubiquitinatedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)subunit glutamate receptor 1(GluR1),which is associated with synaptic plasticity.In addition,elevated levels of USP47 were found in epileptic mice,and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures.To summarize,we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation.Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
基金supported by the National Natural Science Foundation of China(82201667,82371195,and 82304474)the Research Fund of Jianghan University(2023JCYJ15).
文摘Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes.However,its precise role and mechanism of action in stress susceptibility remain elusive.In this study,we found a significant reduction in GADD45B expression specifically in the ventral,but not the dorsal hippocampal CA1(dCA1)of stress-susceptible mice.Furthermore,we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation(LTP)in the ventral hippocampal CA1(vCA1).Importantly,through pharmacological inhibition using the NMDA receptor antagonist MK801,we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP.Collectively,these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
