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
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(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
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
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
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
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
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
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
Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate...Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.展开更多
We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters i...We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters in graphene and F_(16)CuPc channels,separately.This process facilitates fast-switching plasticity by altering charge carriers in the separated channels.The complementary neural network for image recognition of Fashion-MNIST dataset was constructed using the matched relative amplitude and plasticity properties of the GFST dominated by holes or electrons to improve the weight regulation and recognition accuracy,achieving a pattern recognition accuracy of 83.23%.These results provide new insights to the construction of future neuromorphic systems.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
Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistor...Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistors(EGOTs)offer significant advantages as neuromorphic devices due to their ultra-low operation voltages,minimal hardwired connectivity,and similar operation environment as electrophysiology.Meanwhile,ionic–electronic coupling and the relatively low elastic moduli of organic channel materials make EGOTs suitable for interfacing with biology.This review presents an overview of the device architectures based on organic electrochemical transistors and organic field-effect transistors.Furthermore,we review the requirements of low energy consumption and tunable synaptic plasticity of EGOTs in emulating biological synapses and how they are affected by the organic materials,electrolyte,architecture,and operation mechanism.In addition,we summarize the basic operation principle of biological sensory systems and the recent progress of EGOTs as a building block in artificial systems.Finally,the current challenges and future development of the organic neuromorphic devices are discussed.展开更多
Artificial sensory systems(ASS)are pivotal to next-generation extended reality technologies,now evolving into flexible platforms for comfortable wear and immersive user experiences,while ensuring high performance and ...Artificial sensory systems(ASS)are pivotal to next-generation extended reality technologies,now evolving into flexible platforms for comfortable wear and immersive user experiences,while ensuring high performance and operational reliability.To address these demands,metal-based nanoparticles(NPs),such as noble metal,oxide,and multi-elemental NPs,have been extensively incorporated into functional materials of sensory and synaptic devices due to their tunable optical,electrical,and chemical properties,enhancing sensory precision,stability,and environmental adaptability.However,traditional NP fabrication methods often involve complex processing,residual contaminants,and scalability issues,limiting their effectiveness in ASS applications.State-of-the-art laser ablation in liquids(LAL)presents a promising alternative,offering scalable production of surfactant-free NPs with customizable physicochemical properties,though their application in electronics remains underexplored.This review delves into the transformative potential of LAL-fabricated NPs in ASS,covering the fundamental mechanisms of LAL,the role of process parameters,the derivative strategies for size modulation,the diversity of metal-based NPs,their applications in sensory and synaptic devices,and the challenges and perspectives for meeting industrial standards.Bridging the gap between LAL and ASS is poised to revolutionize both industrial manufacturing and academic research by offering scalable solutions to overcome intrinsic tradeoffs between flexibility and performance,fostering innovations in human-centric,immersive electronics.展开更多
Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system...Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system,and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.Methods Colocalization analysis of APP with specific tagged proteins in the TGN,ensolysosomal system,and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP.APP,β-site amyloid precursor protein cleaving enzyme 1(BACE1)expressions,and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.Results APP localization was reduced in the TGN,early endosomes,late endosomes,and lysosomes,whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons.Moreover,Arl5b(ADP-ribosylation factor 5b),a protein responsible for transporting APP from the TGN to early endosomes,was upregulated by SV2A.SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis.In addition,products of APP amyloid degradation,including sAPPβ,Aβ1-42,and Aβ1-40,were decreased in SV2A-overexpressed cells.Conclusion These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway,which slows APP amyloid degradation.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
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 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 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 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 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 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 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 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(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 Natural Science Foundation of China(32394032,82201699,and 82221001)the Natural Science Foundation of Zhejiang Province(LTGD24H250001)+1 种基金the Kay R&D Program of Shaanxi Province(2023-YBSF-093),the Young Talent Fund of University Association for Science and Technology in Shaanxi(20220306)the Joint Founding Project of Innovation Research Institute,Xijing Hospital(LHJJ24JH02).
文摘Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
基金supported by the Shenzhen Science and Technology Program(No.JCYJ20210324121002008)the National Science Fund for Distinguished Young Scholars of China(No.T2125005)+5 种基金the National Key R&D Program of China(Nos.2022YFE0198200,2022YFA1204500,and 2022YFA1204504)the Natural Science Foundation of Tianjin(Nos.22JCYBJC01290 and 23JCQNJC01440)the Key Project of Natural Science Foundation of Tianjin(No.22JCZDJC00120)the Fundamental Research Funds for the Central Universities,Nankai University(Nos.BEG124901 and BEG124401)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110319)the Key Science and Technology Program of Henan Province(No.242102210171).
文摘We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters in graphene and F_(16)CuPc channels,separately.This process facilitates fast-switching plasticity by altering charge carriers in the separated channels.The complementary neural network for image recognition of Fashion-MNIST dataset was constructed using the matched relative amplitude and plasticity properties of the GFST dominated by holes or electrons to improve the weight regulation and recognition accuracy,achieving a pattern recognition accuracy of 83.23%.These results provide new insights to the construction of future neuromorphic systems.
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.
基金financial support by the self-supporting project of Pazhou Lab(No.PZL2023ZZ0011)by National Key R&D Program of China(No.2019YFA0904801).
文摘Rapid development of artificial intelligence requires the implementation of hardware systems with bioinspired parallel information processing and presentation and energy efficiency.Electrolyte-gated organic transistors(EGOTs)offer significant advantages as neuromorphic devices due to their ultra-low operation voltages,minimal hardwired connectivity,and similar operation environment as electrophysiology.Meanwhile,ionic–electronic coupling and the relatively low elastic moduli of organic channel materials make EGOTs suitable for interfacing with biology.This review presents an overview of the device architectures based on organic electrochemical transistors and organic field-effect transistors.Furthermore,we review the requirements of low energy consumption and tunable synaptic plasticity of EGOTs in emulating biological synapses and how they are affected by the organic materials,electrolyte,architecture,and operation mechanism.In addition,we summarize the basic operation principle of biological sensory systems and the recent progress of EGOTs as a building block in artificial systems.Finally,the current challenges and future development of the organic neuromorphic devices are discussed.
基金supported by the Nano&Material Technology Development Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(Grant Nos.RS-2024-00403639 and RS2024-00411904)。
文摘Artificial sensory systems(ASS)are pivotal to next-generation extended reality technologies,now evolving into flexible platforms for comfortable wear and immersive user experiences,while ensuring high performance and operational reliability.To address these demands,metal-based nanoparticles(NPs),such as noble metal,oxide,and multi-elemental NPs,have been extensively incorporated into functional materials of sensory and synaptic devices due to their tunable optical,electrical,and chemical properties,enhancing sensory precision,stability,and environmental adaptability.However,traditional NP fabrication methods often involve complex processing,residual contaminants,and scalability issues,limiting their effectiveness in ASS applications.State-of-the-art laser ablation in liquids(LAL)presents a promising alternative,offering scalable production of surfactant-free NPs with customizable physicochemical properties,though their application in electronics remains underexplored.This review delves into the transformative potential of LAL-fabricated NPs in ASS,covering the fundamental mechanisms of LAL,the role of process parameters,the derivative strategies for size modulation,the diversity of metal-based NPs,their applications in sensory and synaptic devices,and the challenges and perspectives for meeting industrial standards.Bridging the gap between LAL and ASS is poised to revolutionize both industrial manufacturing and academic research by offering scalable solutions to overcome intrinsic tradeoffs between flexibility and performance,fostering innovations in human-centric,immersive electronics.
基金supported by grants from the State Key Program of the National Natural Science Foundation of China(grant number 82030064)Beijing Hospital Authority Youth Program(grant number QML20230812)+2 种基金Research and Development Foundation of Capital Medical University(grant number PYZ23052)National Natural Science Youth Cultivation Project of Xuanwu Hospital,Capital Medical University(grant number QNPY202317)Capital Medical University Research and Cultivation Fund(grant number PYZ23049).
文摘Objective To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A(SV2A)influences the distribution of amyloid precursor protein(APP)in the trans-Golgi network(TGN),endolysosomal system,and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.Methods Colocalization analysis of APP with specific tagged proteins in the TGN,ensolysosomal system,and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP.APP,β-site amyloid precursor protein cleaving enzyme 1(BACE1)expressions,and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.Results APP localization was reduced in the TGN,early endosomes,late endosomes,and lysosomes,whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons.Moreover,Arl5b(ADP-ribosylation factor 5b),a protein responsible for transporting APP from the TGN to early endosomes,was upregulated by SV2A.SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis.In addition,products of APP amyloid degradation,including sAPPβ,Aβ1-42,and Aβ1-40,were decreased in SV2A-overexpressed cells.Conclusion These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway,which slows APP amyloid degradation.
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.
