An indium-zinc-oxide （IZO） based ionic/electronic hybrid synaptic transistor gated by field-configurable nanogranular SiO2 films was reported. The devices exhibited a high current ON/OFF ratio of above 107, a high e...An indium-zinc-oxide （IZO） based ionic/electronic hybrid synaptic transistor gated by field-configurable nanogranular SiO2 films was reported. The devices exhibited a high current ON/OFF ratio of above 107, a high electron mobility of ～14 cm2 V^-1 s^-1 and a low subthreshold swing of ～80 mV/decade. The gate bias would modulate the interplay between protons and electrons at the channel/dielectric interface. Due to the dynamic modulation of the transient protons flux within the nanogranular SiO2 films, the channel current would be modified dynamically. Short-term synaptic plasticities, such as short-term potentiation and short- term depression, were mimicked on the proposed IZO synaptic transistor. The results indicate that the synaptic transistor proposed here has potential applications in future neuromorphic devices.展开更多
Multi-terminal electric-double-layer transistors have recently attracted extensive interest in terms of mimicking synaptic and neural functions.In this work,an Ion-Gel gated graphene synaptic transistor was proposed t...Multi-terminal electric-double-layer transistors have recently attracted extensive interest in terms of mimicking synaptic and neural functions.In this work,an Ion-Gel gated graphene synaptic transistor was proposed to mimic the essential synaptic behaviors by exploiting the bipolar property of graphene and the ionic conductivity of Ion-Gel.The Ion-Gel dielectrics were deposited onto the graphene film by the spin coating process.We consider the top gate and graphene channel as a presynaptic and postsynaptic terminal,respectively.Basic synaptic functions were successfully mimicked,including the excitatory postsynaptic current(EPSC),the effect of spike amplitude and duration on EPSC,and paired-pulse facilitation(PPF).This work may facilitate the application of graphene synaptic transistors in flexible electronics.展开更多
Synaptotagmin 7(Syt7), a presynaptic calcium sensor, has a significant role in the facilitation in shortterm synaptic plasticity: Syt7 knock out mice show a significant reduction in the facilitation. The functional im...Synaptotagmin 7(Syt7), a presynaptic calcium sensor, has a significant role in the facilitation in shortterm synaptic plasticity: Syt7 knock out mice show a significant reduction in the facilitation. The functional importance of short-term synaptic plasticity such as facilitation is not well understood. In this study, we attempt to investigate the potential functional relationship between the short-term synaptic plasticity and postsynaptic response by developing a mathematical model that captures the responses of both wild-type and Syt7 knock-out mice. We then studied the model behaviours of wild-type and Syt7 knock-out mice in response to multiple input action potentials. These behaviors could establish functional importance of short-term plasticity in regulating the postsynaptic response and related synaptic properties. In agreement with previous modeling studies, we show that release sites are governed by non-uniform release probabilities of neurotransmitters. The structure of non-uniform release of neurotransmitters makes shortterm synaptic plasticity to act as a high-pass filter. We also propose that Syt7 may be a modulator for the long-term changes of postsynaptic response that helps to train the target frequency of the filter. We have developed a mathematical model of short-term plasticity which explains the experimental data.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
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
Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive...Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive.Herein,we found that lumbar 5 spinal nerve ligation(SNL)in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus.The Neurl1 expression in the hippocampal CA1 was decreased after SNL.And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2.Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment,and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL.Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity.The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1.Collectively,the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and,in turn,repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.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
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly m...Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.展开更多
Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the me...Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182).展开更多
Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor （NMDAR） signaling pathway to establish whether this plays a role in synaptic plasticity imp...Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor （NMDAR） signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H＆E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits （NR1, NR2A, and NR2B） and related signaling molecules （CaZ＋/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein） were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.展开更多
Cerebral ischemia activates an endogenous repair program that induces plastic changes in neurons. In this study, we investigated the effects of environmental enrichment on spatial learning and memory as well as on syn...Cerebral ischemia activates an endogenous repair program that induces plastic changes in neurons. In this study, we investigated the effects of environmental enrichment on spatial learning and memory as well as on synaptic remodeling in a mouse model of chronic cerebral ischemia, produced by subjecting adult male C57 BL/6 mice to permanent left middle cerebral artery occlusion. Three days postoperatively, mice were randomly assigned to the environmental enrichment and standard housing groups. Mice in the standard housing group were housed and fed a standard diet. Mice in the environmental enrichment group were housed in a cage with various toys and fed a standard diet. Then, 28 days postoperatively, spatial learning and memory were tested using the Morris water maze. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 in the hippocampus were analyzed by western blot assay. The number of synapses was evaluated by electron microscopy. In the water maze test, mice in the environmental enrichment group had a shorter escape latency, traveled markedly longer distances, spent more time in the correct quadrant(northeast zone), and had a higher frequency of crossings compared with the standard housing group. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 were substantially upregulated in the hippocampus in the environmental enrichment group compared with the standard housing group. Furthermore, electron microscopy revealed that environmental enrichment increased the number of synapses in the hippocampal CA1 region. Collectively, these findings suggest that environmental enrichment ameliorates the spatial learning and memory impairment induced by permanent middle cerebral artery occlusion. Environmental enrichment in mice with cerebral ischemia likely promotes cognitive recovery by inducing plastic changes in synapses.展开更多
With key roles in essential brain functions ranging from the long-term potentiation(LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor(NMDAR) can be considered as one of the fundamental glutamate recept...With key roles in essential brain functions ranging from the long-term potentiation(LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor(NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca^(2+),postsynaptic density 95(PSD-95),calcium/calmodulin-dependent protein kinase II(Ca MK II),protein kinase A(PKA),mitogen-activated protein kinase(MAPK) and cyclic adenosine monophosphate(c AMP) responsive element binding protein(CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.展开更多
Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its ex-pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic pl...Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its ex-pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged （22-24 month old） rats was significantly lower than that in young （1 month old） and adult （4 months old） rats. Ex- pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.展开更多
Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulati...Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cog-nition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China(approval No. TJ-A20151102) on July 11, 2015.展开更多
In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic ...In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanfi （ST36） and Yanglingquan （GB34）. In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold （paw withdrawal latency） was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanfi and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.展开更多
To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging ...To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging were used in slice preparations of the anterior cingulate cortex （ACC） from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials （LFPs） and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation （LTP） and changes in LTP magnitude were also evaluated. We found that under naive conditions, the current sink was initially generated in layer Ⅵ, then spread to layer Ⅴ and finally confined to layers Ⅱ-Ⅲ. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers （Ⅴ-Ⅵ） to superficial layers （Ⅱ-Ⅲ） where intra- and extra- cortical inputs terminate. In the ACC slices from rats in an inflamed state （for 2 h） caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed,showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naive and saline controls. The change was more distinct in the superficial layers （Ⅱ-Ⅲ） than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers Ⅱ-Ⅲ by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.展开更多
Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cogniti...Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cognitive.The etiology of SCZ is thought to be multifactorial and poorly understood.Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ.Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ.Many factors,including synaptic structure changes,aberrant expression of plasticityrelated genes,and abnormal synaptic transmission,may influence synaptic plasticity and play vital roles in SCZ.In this article,we briefly summarize the morphology of the synapse,the neurobiology of synaptic plasticity,and the role of synaptic plasticity,and review potential mechanisms underlying abnormal synaptic plasticity in SCZ.These abnormalities involve dendritic spines,postsynaptic density,and long-term potentiation-like plasticity.We also focus on cognitive dysfunction,which reflects impaired connectivity in SCZ.Additionally,the potential targets for the treatment of SCZ are discussed in this article.Therefore,understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.展开更多
The prefrontal cortex （PFC） is thought to store the traces for a type of long-term memory - the memory that determines the temporal structure of behavior often termed a ＂rule＂ or ＂strategy＂. Long-term synaptic p...The prefrontal cortex （PFC） is thought to store the traces for a type of long-term memory - the memory that determines the temporal structure of behavior often termed a ＂rule＂ or ＂strategy＂. Long-term synaptic plasticity might serve as an underlying cellular mechanism for this type of memory. We therefore studied the induction of synaptic plasticity in rat PFC neurons, maintained in vitro, with special emphasis on the functionally important neuromodulator dopamine. First, the induction of long-term potentiation （LTP） was facilitated in the presence of tonic/background dopamine in the bath, and the dose-dependency of this background dopamine followed an ＂inverted-U＂ function, where too high or too low dopamine levels could not facilitate LTP. Second, the induction of long-term depression （LTD） by low-frequency stimuli appeared to be independent of background dopamine, but required endogenous, phasically-released dopamine during the stimuli. Blockade of dopamine receptors during the stimuli and exaggeration of the effect of this endogenouslyreleased dopamine by inhibition of dopamine transporter activity both blocked LTD. Thus, LTD induction also followed an inverted-U function in its dopamine-dependency. We conclude that PFC synaptic plasticity is powerfully modulated by dopamine through inverted-U-shaped dose-dependency.展开更多
基金supported by the National Program on Key Basic Research Project (No.2012CB933004)the Zhejiang Provincial Natural Science Foundation of China (No.LY14A040009)the Ningbo Natural Science Foundation (No.2013A610001)
文摘An indium-zinc-oxide （IZO） based ionic/electronic hybrid synaptic transistor gated by field-configurable nanogranular SiO2 films was reported. The devices exhibited a high current ON/OFF ratio of above 107, a high electron mobility of ～14 cm2 V^-1 s^-1 and a low subthreshold swing of ～80 mV/decade. The gate bias would modulate the interplay between protons and electrons at the channel/dielectric interface. Due to the dynamic modulation of the transient protons flux within the nanogranular SiO2 films, the channel current would be modified dynamically. Short-term synaptic plasticities, such as short-term potentiation and short- term depression, were mimicked on the proposed IZO synaptic transistor. The results indicate that the synaptic transistor proposed here has potential applications in future neuromorphic devices.
文摘Multi-terminal electric-double-layer transistors have recently attracted extensive interest in terms of mimicking synaptic and neural functions.In this work,an Ion-Gel gated graphene synaptic transistor was proposed to mimic the essential synaptic behaviors by exploiting the bipolar property of graphene and the ionic conductivity of Ion-Gel.The Ion-Gel dielectrics were deposited onto the graphene film by the spin coating process.We consider the top gate and graphene channel as a presynaptic and postsynaptic terminal,respectively.Basic synaptic functions were successfully mimicked,including the excitatory postsynaptic current(EPSC),the effect of spike amplitude and duration on EPSC,and paired-pulse facilitation(PPF).This work may facilitate the application of graphene synaptic transistors in flexible electronics.
基金supported by a grant from Lincoln University,New Zealand
文摘Synaptotagmin 7(Syt7), a presynaptic calcium sensor, has a significant role in the facilitation in shortterm synaptic plasticity: Syt7 knock out mice show a significant reduction in the facilitation. The functional importance of short-term synaptic plasticity such as facilitation is not well understood. In this study, we attempt to investigate the potential functional relationship between the short-term synaptic plasticity and postsynaptic response by developing a mathematical model that captures the responses of both wild-type and Syt7 knock-out mice. We then studied the model behaviours of wild-type and Syt7 knock-out mice in response to multiple input action potentials. These behaviors could establish functional importance of short-term plasticity in regulating the postsynaptic response and related synaptic properties. In agreement with previous modeling studies, we show that release sites are governed by non-uniform release probabilities of neurotransmitters. The structure of non-uniform release of neurotransmitters makes shortterm synaptic plasticity to act as a high-pass filter. We also propose that Syt7 may be a modulator for the long-term changes of postsynaptic response that helps to train the target frequency of the filter. We have developed a mathematical model of short-term plasticity which explains the experimental data.
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 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 National Natural Science Foundation of China(82171237,82471246,and 82401462)the Natural Science Foundation of Henan Province,China(242300420381).
文摘Neuropathic pain is frequently comorbidity with cognitive deficits.Neuralized1(Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory.However,the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive.Herein,we found that lumbar 5 spinal nerve ligation(SNL)in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus.The Neurl1 expression in the hippocampal CA1 was decreased after SNL.And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2.Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment,and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL.Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity.The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1.Collectively,the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and,in turn,repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
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.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
文摘Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.
基金supported by the National Natural Science Foundation of China,No.81571038,81771145(both to YZ)
文摘Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182).
基金supported by the National Natural Science Foundation of China(No.81172620)
文摘Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor （NMDAR） signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H＆E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits （NR1, NR2A, and NR2B） and related signaling molecules （CaZ＋/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein） were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.
基金supported by the National Natural Science Foundation of China,No.81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Cerebral ischemia activates an endogenous repair program that induces plastic changes in neurons. In this study, we investigated the effects of environmental enrichment on spatial learning and memory as well as on synaptic remodeling in a mouse model of chronic cerebral ischemia, produced by subjecting adult male C57 BL/6 mice to permanent left middle cerebral artery occlusion. Three days postoperatively, mice were randomly assigned to the environmental enrichment and standard housing groups. Mice in the standard housing group were housed and fed a standard diet. Mice in the environmental enrichment group were housed in a cage with various toys and fed a standard diet. Then, 28 days postoperatively, spatial learning and memory were tested using the Morris water maze. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 in the hippocampus were analyzed by western blot assay. The number of synapses was evaluated by electron microscopy. In the water maze test, mice in the environmental enrichment group had a shorter escape latency, traveled markedly longer distances, spent more time in the correct quadrant(northeast zone), and had a higher frequency of crossings compared with the standard housing group. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 were substantially upregulated in the hippocampus in the environmental enrichment group compared with the standard housing group. Furthermore, electron microscopy revealed that environmental enrichment increased the number of synapses in the hippocampal CA1 region. Collectively, these findings suggest that environmental enrichment ameliorates the spatial learning and memory impairment induced by permanent middle cerebral artery occlusion. Environmental enrichment in mice with cerebral ischemia likely promotes cognitive recovery by inducing plastic changes in synapses.
基金supported by the National Natural Science Foundation of China(61401497)
文摘With key roles in essential brain functions ranging from the long-term potentiation(LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor(NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca^(2+),postsynaptic density 95(PSD-95),calcium/calmodulin-dependent protein kinase II(Ca MK II),protein kinase A(PKA),mitogen-activated protein kinase(MAPK) and cyclic adenosine monophosphate(c AMP) responsive element binding protein(CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.
基金funded by the National Natural Science Foundation of China,No.81071009,31200740,81271412the International S & T Cooperation Project of the Ministry of S & T of China,No.2010DFR30850+1 种基金the People’s Livelihood S & T Project,the Bureau of S & T of Dalian,No.2010E11SF008,2011E12SF030the Doctoral Fund of S & T Department of Liaoning Province,No.20121109
文摘Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its ex-pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged （22-24 month old） rats was significantly lower than that in young （1 month old） and adult （4 months old） rats. Ex- pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.
基金supported by the National Natural Science Foundation of China,No.81272156(to TCG)
文摘Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cog-nition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China(approval No. TJ-A20151102) on July 11, 2015.
基金supported by the National Natural Science Foundation of China,No.30472241,90709031 and 30973796the National Basic Research Program of China for Traditional Chinese Medicine Theory("973" Program),No.2007CB512505+1 种基金the Natural Foundation of Hainan Province(No.310054)a grant from the Health Department of Hainan Province(QiongWei 2010-45)
文摘In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanfi （ST36） and Yanglingquan （GB34）. In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold （paw withdrawal latency） was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanfi and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.
基金supported by grants from the National Basic Research Development ProgramMinistry of Science and Technology of China(2013CB835100+3 种基金2013BAI04B04)the National Natural Science Foundation of China(8107089981171049)a Military Project of China(AWS12J004)
文摘To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging were used in slice preparations of the anterior cingulate cortex （ACC） from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials （LFPs） and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation （LTP） and changes in LTP magnitude were also evaluated. We found that under naive conditions, the current sink was initially generated in layer Ⅵ, then spread to layer Ⅴ and finally confined to layers Ⅱ-Ⅲ. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers （Ⅴ-Ⅵ） to superficial layers （Ⅱ-Ⅲ） where intra- and extra- cortical inputs terminate. In the ACC slices from rats in an inflamed state （for 2 h） caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed,showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naive and saline controls. The change was more distinct in the superficial layers （Ⅱ-Ⅲ） than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers Ⅱ-Ⅲ by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.
基金Supported by National Natural Science Foundation of China,No. 81971943, No. 81772196, No. 31470264, No. 81271820, No. 30870789 and No. 30300117Stanley Foundation from the Stanley Medical Research Institute (SMRI),United States,No. 06R-1366 (to Dr. Zhu F)Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University,No. TFJC 2018002
文摘Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cognitive.The etiology of SCZ is thought to be multifactorial and poorly understood.Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ.Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ.Many factors,including synaptic structure changes,aberrant expression of plasticityrelated genes,and abnormal synaptic transmission,may influence synaptic plasticity and play vital roles in SCZ.In this article,we briefly summarize the morphology of the synapse,the neurobiology of synaptic plasticity,and the role of synaptic plasticity,and review potential mechanisms underlying abnormal synaptic plasticity in SCZ.These abnormalities involve dendritic spines,postsynaptic density,and long-term potentiation-like plasticity.We also focus on cognitive dysfunction,which reflects impaired connectivity in SCZ.Additionally,the potential targets for the treatment of SCZ are discussed in this article.Therefore,understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.
文摘The prefrontal cortex （PFC） is thought to store the traces for a type of long-term memory - the memory that determines the temporal structure of behavior often termed a ＂rule＂ or ＂strategy＂. Long-term synaptic plasticity might serve as an underlying cellular mechanism for this type of memory. We therefore studied the induction of synaptic plasticity in rat PFC neurons, maintained in vitro, with special emphasis on the functionally important neuromodulator dopamine. First, the induction of long-term potentiation （LTP） was facilitated in the presence of tonic/background dopamine in the bath, and the dose-dependency of this background dopamine followed an ＂inverted-U＂ function, where too high or too low dopamine levels could not facilitate LTP. Second, the induction of long-term depression （LTD） by low-frequency stimuli appeared to be independent of background dopamine, but required endogenous, phasically-released dopamine during the stimuli. Blockade of dopamine receptors during the stimuli and exaggeration of the effect of this endogenouslyreleased dopamine by inhibition of dopamine transporter activity both blocked LTD. Thus, LTD induction also followed an inverted-U function in its dopamine-dependency. We conclude that PFC synaptic plasticity is powerfully modulated by dopamine through inverted-U-shaped dose-dependency.
