Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse functi...Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.展开更多
Organic electrochemical transistors have emerged as a solution for artificial synapses that mimic the neural functions of the brain structure,holding great potentials to break the bottleneck of von Neumann architectur...Organic electrochemical transistors have emerged as a solution for artificial synapses that mimic the neural functions of the brain structure,holding great potentials to break the bottleneck of von Neumann architectures.However,current artificial synapses rely primarily on electrical signals,and little attention has been paid to the vital role of neurotransmitter-mediated artificial synapses.Dopamine is a key neurotransmitter associated with emotion regulation and cognitive processes that needs to be monitored in real time to advance the development of disease diagnostics and neuroscience.To provide insights into the development of artificial synapses with neurotransmitter involvement,this review proposes three steps towards future biomimic and bioinspired neuromorphic systems.We first summarize OECT-based dopamine detection devices,and then review advances in neurotransmitter-mediated artificial synapses and resultant advanced neuromorphic systems.Finally,by exploring the challenges and opportunities related to such neuromorphic systems,we provide a perspective on the future development of biomimetic and bioinspired neuromorphic systems.展开更多
The crossmodal interaction of different senses,which is an important basis for learning and memory in the human brain,is highly desired to be mimicked at the device level for developing neuromorphic crossmodal percept...The crossmodal interaction of different senses,which is an important basis for learning and memory in the human brain,is highly desired to be mimicked at the device level for developing neuromorphic crossmodal perception,but related researches are scarce.Here,we demonstrate an optoelectronic synapse for vision-olfactory crossmodal perception based on MXene/violet phosphorus(VP)van der Waals heterojunctions.Benefiting from the efficient separation and transport of photogenerated carriers facilitated by conductive MXene,the photoelectric responsivity of VP is dramatically enhanced by 7 orders of magnitude,reaching up to 7.7 A W^(−1).Excited by ultraviolet light,multiple synaptic functions,including excitatory postsynaptic currents,pairedpulse facilitation,short/long-term plasticity and“learning-experience”behavior,were demonstrated with a low power consumption.Furthermore,the proposed optoelectronic synapse exhibits distinct synaptic behaviors in different gas environments,enabling it to simulate the interaction of visual and olfactory information for crossmodal perception.This work demonstrates the great potential of VP in optoelectronics and provides a promising platform for applications such as virtual reality and neurorobotics.展开更多
Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and syn...Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and synapses.Currently,numerous kinds of OECTs have been developed,while self-healing performance has been neglected in most reported OECTs.In this work,the OECTs using self-healing polymer electrolytes as dielectric layers are proposed.Several important synaptic behaviors are simulated in the OECTs by doping the channel layers with ions from the electrolytes.Benefitting from the dynamic hydrogen bonds in the self-healing polymer electrolytes,the OECTs can successfully maintain their electrical performance and the ability of emulating synaptic behaviors after self-healing compared with the initial state.More significantly,the sublinear spatial summation function is demonstrated in the OECTs and their potential in flexible electronics is also validated.These results suggest that our devices are expected to be a vital component in the development of future wearable and bioimplantable neuromorphic systems.展开更多
Artificial synapses are essential building blocks for neuromorphic electronics.Here,solid polymer electrolyte-gated artificial synapses(EGASs)were fabricated using ITO fibers as channels,which possess an ultra-high se...Artificial synapses are essential building blocks for neuromorphic electronics.Here,solid polymer electrolyte-gated artificial synapses(EGASs)were fabricated using ITO fibers as channels,which possess an ultra-high sensitivity of 5 m V and a long-term memory time exceeding 3 min.Notably,digitally printed ITO-fiber arrays exhibit an ultra-high transmittance of approximately 99.67%.Biological synaptic plasticity,such as excitatory postsynaptic current,paired-pulse facilitation,spike frequency-dependent plasticity,and synaptic potentiation and depression,were successfully mimicked using the EGASs.Based on the synaptic properties of the EGASs,an artificial neural network was constructed to perform supervised learning using the Fashion-MNIST dataset,achieving high pattern recognition rate(82.39%)due to the linear and symmetric synaptic plasticity.This work provides insights into high-sensitivity artificial synapses for future neuromorphic computing.展开更多
Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function....Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.展开更多
Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have ...Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.展开更多
Objective and methods To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. Result...Objective and methods To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. Results Normal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the ThS-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord. Conclusion Synaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an import,ant role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.展开更多
α-Synuclein causes synaptic pathologies in several neurodegenerative diseases：Parkinson’s disease（PD）is a neurodegenerative disease that impacts the lives of millions of people worldwide.A pathological hallmark o...α-Synuclein causes synaptic pathologies in several neurodegenerative diseases：Parkinson’s disease（PD）is a neurodegenerative disease that impacts the lives of millions of people worldwide.A pathological hallmark of PD,as well as dementia with Lewy bodies（DLB）and several Alzheimer’s disease variants,is the appearanceof intracellular inclusions called Lewy bodies, which contain high levels of aggregated α-synuclein,展开更多
For the mammalian brain to process and decipher the rich panoply of sounds that abound in the world, nature has evolved an elegant collection of neural circuits dedicated to this task. Indeed, the complexity, variety ...For the mammalian brain to process and decipher the rich panoply of sounds that abound in the world, nature has evolved an elegant collection of neural circuits dedicated to this task. Indeed, the complexity, variety and number of neural pathways devoted to computing auditory information is unique among sensory modalities （Kaas, 2008）. After the initial sensorineural encoding of sound at the level of the cochlea, auditory information is processed in several lower brainstem centers and eventually converges in the midbrain, at the level of the inferior colliculus （Wenstrup, 2005）, Subsequently, auditory information is transferred through the thalamus, the medial geniculate body, and then the auditory cortex （Winer et al., 2005; Razak and Fuzessery, 2010; Hackett, 2011; Lee and Sherman, 2011; Lee and Winer, 2011;展开更多
Photonic synapses combining photosensitivity and synaptic function can efficiently perceive and memorize visual information,making them crucial for the development of artificial vision systems.However,the development ...Photonic synapses combining photosensitivity and synaptic function can efficiently perceive and memorize visual information,making them crucial for the development of artificial vision systems.However,the development of high-performance photonic synapses with low power consumption and rapid optical erasing ability remains challenging.Here,we propose a photon-modulated charging/discharging mechanism for self-powered photonic synapses.The current hysteresis enables the devices based on CsPbBr3/solvent/carbon nitride multilayer architecture to emulate synaptic behaviors,such as excitatory postsynaptic currents,paired-pulse facilitation,and long/short-term memory.Intriguingly,the unique radiation direction-dependent photocurrent endows the photonic synapses with the capability of optical writing and rapid optical erasing.Moreover,the photonic synapses exhibit exceptional performance in contrast enhancement and noise reduction owing to the notable synaptic plasticity.In simulations based on artificial neural network(ANN)algorithms,the pre-processing by our photonic synapses improves the recognition rate of handwritten digit from 11.4%(200 training epochs)to 85%(~60 training epochs).Furthermore,due to the excellent feature extraction and memory capability,an array based on the photonic synapses can imitate facial recognition of human retina without the assistance of ANN.展开更多
Recently,artificial synapses involving an electrochemical reaction of Li-ion have been attributed to have remarkable synaptic properties.Three-terminal synaptic transistors utilizing Li-ion intercalation exhibits reli...Recently,artificial synapses involving an electrochemical reaction of Li-ion have been attributed to have remarkable synaptic properties.Three-terminal synaptic transistors utilizing Li-ion intercalation exhibits reliable synaptic characteristics by exploiting the advantage of nondistributed weight updates owing to stable ion migrations.However,the three-terminal configurations with large and complex structures impede the crossbar array implementation required for hardware neuromorphic systems.Meanwhile,achieving adequate synaptic performances through effective Li-ion intercalation in vertical two-terminal synaptic devices for array integration remains challenging.Here,two-terminal Au/LixCoO_(2)/Pt artificial synapses are proposed with the potential for practical implementation of hardware neural networks.The Au/LixCoO_(2)/Pt devices demonstrated extraordinary neuromorphic behaviors based on a progressive dearth of Li in LixCoO_(2)films.The intercalation and deintercalation of Li-ion inside the films are precisely controlled over the weight control spike,resulting in improved weight control functionality.Various types of synaptic plasticity were imitated and assessed in terms of key factors such as nonlinearity,symmetricity,and dynamic range.Notably,the LixCoO_(2)-based neuromorphic system outperformed three-terminal synaptic transistors in simulations of convolutional neural networks and multilayer perceptrons due to the high linearity and low programming error.These impressive performances suggest the vertical two-terminal Au/LixCoO_(2)/Pt artificial synapses as promising candidates for hardware neural networks.展开更多
The neuromorphic systems for sound perception is under highly demanding for the future bioinspired electronics and humanoid robots.However,the sound perception based on volume,tone and timbre remains unknown.Herein,or...The neuromorphic systems for sound perception is under highly demanding for the future bioinspired electronics and humanoid robots.However,the sound perception based on volume,tone and timbre remains unknown.Herein,organic optoelectronic synapses(OOSs)are constructed for unprecedented sound recognition.The volume,tone and timbre of sound can be regulated appropriately by the input signal of voltages,frequencies and light intensities of OOSs,according to the amplitude,frequency,and waveform of the sound.The quantitative relation between recognition factor(ζ)and postsynaptic current(I=I_(light)−I_(dark))is established to achieve sound perception.Interestingly,the bell sound for University of Chinese Academy of Sciences is recognized with an accuracy of 99.8%.The mechanism studies reveal that the impedance of the interfacial layers play a critical role in the synaptic performances.This contribution presents unprecedented artificial synapses for sound perception at hardware levels.展开更多
Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audit...Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.展开更多
Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of f...Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.展开更多
In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation （0.52 1.08 W/kg） was delivered to 8...In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation （0.52 1.08 W/kg） was delivered to 8-week-old Wistar rats 2 hours per day for 1 month, behavioral changes were examined using the Morris water maze. Compared with the sham-irradiated rats, the irradiated rats exhibited impaired performance. Morphological changes were investigated by examining synaptic ultrastructural changes in the hippocampus. Using the physical dissector technique, the number of pyramidal neurons, the synaptic profiles, and the length of postsynaptic densities in the CA1 region were quantified stereologically. The morphological changes included mitochondrial degenerations, fewer synapses, and shorter postsynaptic densities in the radiated rats. These findings indicate that mobile phone radiation can significantly impair spatial learning and reference memory and induce morphological changes in the hippocampal CA1 region.展开更多
The multiple ferroelectric polarization tuned by external electric field could be used to simulate the biological synaptic weight. Ferroelectric synaptic devices have two advantages compared with other reported ones: ...The multiple ferroelectric polarization tuned by external electric field could be used to simulate the biological synaptic weight. Ferroelectric synaptic devices have two advantages compared with other reported ones: One is that the intrinsic switching of ferroelectric domains without invoking of defect migration as in resistive oxides, contributes reliable performance in these ferroelectric synapses. Another tremendous advantage is the extremely low energy consumption because the ferroelectric polarization is manipulated by electric field which eliminates the Joule heating by current as in magnetic and phase change memories. Ferroelectric synapses have potential for the construction of low-energy and effective brain-like intelligent networks. Here we summarize recent pioneering work of ferroelectric synapses involving the structure of ferroelectric tunnel junctions (FTJs), ferroelectric diodes (FDs), and ferroelectric field effect transistors (FeFETs), respectively, and shed light on future work needed to accelerate their application for efficient neural network.展开更多
While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively,little is known of how the functional properties of regenerated synapses compared to those in unlesion...While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively,little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals.This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey,a model system for spinal injury research,in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site.Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials.They also showed the same activity-dependent depression over spike trains.However,regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude.For axons above the lesion site,the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals.However,in this case,there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains.Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery.However,the postsynaptic input was maintained at the unlesioned level using different synaptic properties.Conversely,the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger.This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs.The animal experiments were approved by the Animal Ethics Committee of Cambridge University.展开更多
Neuronal oscillations in the hippocampus are critical for many brain functions including learning and memory.The underlying mechanism of oscillation generation has been extensively investigated in terms of chemical sy...Neuronal oscillations in the hippocampus are critical for many brain functions including learning and memory.The underlying mechanism of oscillation generation has been extensively investigated in terms of chemical synapses and ion channels.Recently,electrical synapses have also been indicated to play important roles,as reported in various brain areas in vivo and in brain slices.However,this issue remains to be further clarified,including in hippocampal networks.Here,using the completely isolated hippocampus,we investigated in vitro the effect of electrical synapses on slow CA1 oscillations(0.5 Hz-1.5 Hz)generated intrinsically by the hippocampus.We found that these oscillations were totally abolished by bath application of a general blocker of gap junctions(carbenoxolone)or a specific blocker of electrical synapses(mefloquine),as determined by whole-cell recordings in both CA1 pyramidal cells and fast-spiking cells.Our findings indicate that electrical synapses are required for the hippocampal generation of slow CA1 oscillations.展开更多
Neuromorphic devices inspired by the human brain have attracted significant attention because of their excellent ability for cognitive and parallel computing.This study presents ZnO-based artificial synapses with pept...Neuromorphic devices inspired by the human brain have attracted significant attention because of their excellent ability for cognitive and parallel computing.This study presents ZnO-based artificial synapses with peptide insulators for the electrical emulation of biological synapses.We demonstrated the dynamic responses of the device under various environmental conditions.The proton-conducting property of the tyrosine-rich peptide enables time-dependent responses under ambient conditions such that various aspects of synaptic behaviors are emulated by the devices.The transition from short-term memory to longterm memory is achieved via electrochemical doping of ZnO by protons.Furthermore,we demonstrate an image classification simulation using a multi-layer perceptron model to evaluate the potential of the device for use in neuromorphic computing.The neural network based on our device achieved a recognition accuracy of 87.47% for the MNIST handwritten digit images.This work proposes a novel device platform inspired by biosystems for brain-mimetic hardware systems.展开更多
基金supported by NIH/NIMH grant R01MH111619(to SQ),R21AG078700(to SQ)Institute of Mental Health Research(IMHR,Level 1 funding,to SQ and DF)institution startup fund from The University of Arizona(to SQ)。
文摘Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.
基金supported by the National Natural Science Foundation of China(Grant No.62074163)Beijing Natural Science Foundation(Grant No.JQ24030).
文摘Organic electrochemical transistors have emerged as a solution for artificial synapses that mimic the neural functions of the brain structure,holding great potentials to break the bottleneck of von Neumann architectures.However,current artificial synapses rely primarily on electrical signals,and little attention has been paid to the vital role of neurotransmitter-mediated artificial synapses.Dopamine is a key neurotransmitter associated with emotion regulation and cognitive processes that needs to be monitored in real time to advance the development of disease diagnostics and neuroscience.To provide insights into the development of artificial synapses with neurotransmitter involvement,this review proposes three steps towards future biomimic and bioinspired neuromorphic systems.We first summarize OECT-based dopamine detection devices,and then review advances in neurotransmitter-mediated artificial synapses and resultant advanced neuromorphic systems.Finally,by exploring the challenges and opportunities related to such neuromorphic systems,we provide a perspective on the future development of biomimetic and bioinspired neuromorphic systems.
基金supported by National Natural Science Foundation of China(No.51902250).
文摘The crossmodal interaction of different senses,which is an important basis for learning and memory in the human brain,is highly desired to be mimicked at the device level for developing neuromorphic crossmodal perception,but related researches are scarce.Here,we demonstrate an optoelectronic synapse for vision-olfactory crossmodal perception based on MXene/violet phosphorus(VP)van der Waals heterojunctions.Benefiting from the efficient separation and transport of photogenerated carriers facilitated by conductive MXene,the photoelectric responsivity of VP is dramatically enhanced by 7 orders of magnitude,reaching up to 7.7 A W^(−1).Excited by ultraviolet light,multiple synaptic functions,including excitatory postsynaptic currents,pairedpulse facilitation,short/long-term plasticity and“learning-experience”behavior,were demonstrated with a low power consumption.Furthermore,the proposed optoelectronic synapse exhibits distinct synaptic behaviors in different gas environments,enabling it to simulate the interaction of visual and olfactory information for crossmodal perception.This work demonstrates the great potential of VP in optoelectronics and provides a promising platform for applications such as virtual reality and neurorobotics.
基金supported by the National Key Research and Development Program of China(No.2021YFA1101303)the National Natural Science Foundation of China(Nos.62074111,62088101)+2 种基金the Science&Technology Foundation of Shanghai(No.20JC1415600)Shanghai Municipal Science and Technology Major Project(No.2021SHZDZX0100)the Innovation Program of Shanghai Municipal Education Commission(No.2021-01-07-0007-E00096)。
文摘Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and synapses.Currently,numerous kinds of OECTs have been developed,while self-healing performance has been neglected in most reported OECTs.In this work,the OECTs using self-healing polymer electrolytes as dielectric layers are proposed.Several important synaptic behaviors are simulated in the OECTs by doping the channel layers with ions from the electrolytes.Benefitting from the dynamic hydrogen bonds in the self-healing polymer electrolytes,the OECTs can successfully maintain their electrical performance and the ability of emulating synaptic behaviors after self-healing compared with the initial state.More significantly,the sublinear spatial summation function is demonstrated in the OECTs and their potential in flexible electronics is also validated.These results suggest that our devices are expected to be a vital component in the development of future wearable and bioimplantable neuromorphic systems.
基金supported by the National Science Fund for Distinguished Young Scholars of China(No.T2125005)the National Key R&D Program of China(Nos.2022YFE0198200,2022YFA1204500,2022YFA1204504)+3 种基金the Shenzhen Science and Technology Project(No.JCYJ20210324121002008)the Natural Science Foundation of Tianjin(Nos.22JCYBJC01290,23JCQNJC01440)the Key Project of Nature Science Foundation of Tianjin(No.22JCZDJC00120)the Fundamental Research Funds for the Central Universities,Nankai University(Nos.BEG124901,BEG124401)。
文摘Artificial synapses are essential building blocks for neuromorphic electronics.Here,solid polymer electrolyte-gated artificial synapses(EGASs)were fabricated using ITO fibers as channels,which possess an ultra-high sensitivity of 5 m V and a long-term memory time exceeding 3 min.Notably,digitally printed ITO-fiber arrays exhibit an ultra-high transmittance of approximately 99.67%.Biological synaptic plasticity,such as excitatory postsynaptic current,paired-pulse facilitation,spike frequency-dependent plasticity,and synaptic potentiation and depression,were successfully mimicked using the EGASs.Based on the synaptic properties of the EGASs,an artificial neural network was constructed to perform supervised learning using the Fashion-MNIST dataset,achieving high pattern recognition rate(82.39%)due to the linear and symmetric synaptic plasticity.This work provides insights into high-sensitivity artificial synapses for future neuromorphic computing.
基金supported by grant PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by"ERDF A way of making Europe"(to RL)supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/21/180501/000064)+3 种基金Universidad de Castilla-La Mancha (2023-GRIN-34187)(to RL).Grant PID201 9-104921RB-I00/MCI/AEI/10.13039/501100011033 (to AGO)the Foundation for Applied Medical Research,the University of Navarra (Pamplona,Spain)for financial supporthe Asociación de Amigos of the University of Navarra for the grant (to SB)Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha (to AMB)
文摘Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.
基金the MRC Laboratory of Molecular Biology (to MR)。
文摘Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.
基金This study was approved by the Uppsala Ethical Committee for Animal Research. It was supported by grants from the Swedish Association of Neurologically Disabled the Swedish Society for Medical Research (project no.950006) and the National Natural Scien
文摘Objective and methods To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. Results Normal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the ThS-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord. Conclusion Synaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an import,ant role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.
基金supported by a grant from National Institutes of Health(NINDS/NIA R01NS078165 to JRM)research funds from the Marine Biological Laboratory(to JRM)a research grant from Horizon 2020 Grant No.In Cure EU Joint Programme-JPND(to LB)
文摘α-Synuclein causes synaptic pathologies in several neurodegenerative diseases：Parkinson’s disease（PD）is a neurodegenerative disease that impacts the lives of millions of people worldwide.A pathological hallmark of PD,as well as dementia with Lewy bodies（DLB）and several Alzheimer’s disease variants,is the appearanceof intracellular inclusions called Lewy bodies, which contain high levels of aggregated α-synuclein,
文摘For the mammalian brain to process and decipher the rich panoply of sounds that abound in the world, nature has evolved an elegant collection of neural circuits dedicated to this task. Indeed, the complexity, variety and number of neural pathways devoted to computing auditory information is unique among sensory modalities （Kaas, 2008）. After the initial sensorineural encoding of sound at the level of the cochlea, auditory information is processed in several lower brainstem centers and eventually converges in the midbrain, at the level of the inferior colliculus （Wenstrup, 2005）, Subsequently, auditory information is transferred through the thalamus, the medial geniculate body, and then the auditory cortex （Winer et al., 2005; Razak and Fuzessery, 2010; Hackett, 2011; Lee and Sherman, 2011; Lee and Winer, 2011;
基金supported by the Natural Science Foundation of Shandong Province(ZR2021YQ32)the China Postdoctoral Science Foundation(2023M740472)+2 种基金the National Natural Science Foundation of China(62175162,62205214,and 61901222)the Taishan Scholars Program of Shandong Province(tsqn201909117)the Special Fund for Science and Technology Innovation Teams of Shanxi Province and Foundation of Shenzhen Science and Technology(20200814100534001).
文摘Photonic synapses combining photosensitivity and synaptic function can efficiently perceive and memorize visual information,making them crucial for the development of artificial vision systems.However,the development of high-performance photonic synapses with low power consumption and rapid optical erasing ability remains challenging.Here,we propose a photon-modulated charging/discharging mechanism for self-powered photonic synapses.The current hysteresis enables the devices based on CsPbBr3/solvent/carbon nitride multilayer architecture to emulate synaptic behaviors,such as excitatory postsynaptic currents,paired-pulse facilitation,and long/short-term memory.Intriguingly,the unique radiation direction-dependent photocurrent endows the photonic synapses with the capability of optical writing and rapid optical erasing.Moreover,the photonic synapses exhibit exceptional performance in contrast enhancement and noise reduction owing to the notable synaptic plasticity.In simulations based on artificial neural network(ANN)algorithms,the pre-processing by our photonic synapses improves the recognition rate of handwritten digit from 11.4%(200 training epochs)to 85%(~60 training epochs).Furthermore,due to the excellent feature extraction and memory capability,an array based on the photonic synapses can imitate facial recognition of human retina without the assistance of ANN.
基金financially supported by National R&D Program(2018M3D1A1058793,2021M3H4A3A02086430)through NRF(National Research Foundation of Korea)funded by the Ministry of Science and ICTsupported by SAIT,Samsung Electronics Co.,Ltd。
文摘Recently,artificial synapses involving an electrochemical reaction of Li-ion have been attributed to have remarkable synaptic properties.Three-terminal synaptic transistors utilizing Li-ion intercalation exhibits reliable synaptic characteristics by exploiting the advantage of nondistributed weight updates owing to stable ion migrations.However,the three-terminal configurations with large and complex structures impede the crossbar array implementation required for hardware neuromorphic systems.Meanwhile,achieving adequate synaptic performances through effective Li-ion intercalation in vertical two-terminal synaptic devices for array integration remains challenging.Here,two-terminal Au/LixCoO_(2)/Pt artificial synapses are proposed with the potential for practical implementation of hardware neural networks.The Au/LixCoO_(2)/Pt devices demonstrated extraordinary neuromorphic behaviors based on a progressive dearth of Li in LixCoO_(2)films.The intercalation and deintercalation of Li-ion inside the films are precisely controlled over the weight control spike,resulting in improved weight control functionality.Various types of synaptic plasticity were imitated and assessed in terms of key factors such as nonlinearity,symmetricity,and dynamic range.Notably,the LixCoO_(2)-based neuromorphic system outperformed three-terminal synaptic transistors in simulations of convolutional neural networks and multilayer perceptrons due to the high linearity and low programming error.These impressive performances suggest the vertical two-terminal Au/LixCoO_(2)/Pt artificial synapses as promising candidates for hardware neural networks.
基金supported by the NSFC(51925306 and 21774130)National Key R&D Program of China(2018FYA 0305800)+2 种基金Key Research Program of the Chinese Academy of Sciences(XDPB08-2)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB28000000)University of Chinese Academy of Sciences.
文摘The neuromorphic systems for sound perception is under highly demanding for the future bioinspired electronics and humanoid robots.However,the sound perception based on volume,tone and timbre remains unknown.Herein,organic optoelectronic synapses(OOSs)are constructed for unprecedented sound recognition.The volume,tone and timbre of sound can be regulated appropriately by the input signal of voltages,frequencies and light intensities of OOSs,according to the amplitude,frequency,and waveform of the sound.The quantitative relation between recognition factor(ζ)and postsynaptic current(I=I_(light)−I_(dark))is established to achieve sound perception.Interestingly,the bell sound for University of Chinese Academy of Sciences is recognized with an accuracy of 99.8%.The mechanism studies reveal that the impedance of the interfacial layers play a critical role in the synaptic performances.This contribution presents unprecedented artificial synapses for sound perception at hardware levels.
基金the National Natural Science Foundation of China(81800901)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(QD2018015)+2 种基金the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030200)the Bureau of International Cooperation,Chinese Academy of Sciences(153D31KYSB20170059).
文摘Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
基金Yantai Science and Technology Development Projects, No. 2008142-5
文摘Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.
基金supported by the Natural Science Foundation of Hebei Province,No. C2007000921
文摘In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation （0.52 1.08 W/kg） was delivered to 8-week-old Wistar rats 2 hours per day for 1 month, behavioral changes were examined using the Morris water maze. Compared with the sham-irradiated rats, the irradiated rats exhibited impaired performance. Morphological changes were investigated by examining synaptic ultrastructural changes in the hippocampus. Using the physical dissector technique, the number of pyramidal neurons, the synaptic profiles, and the length of postsynaptic densities in the CA1 region were quantified stereologically. The morphological changes included mitochondrial degenerations, fewer synapses, and shorter postsynaptic densities in the radiated rats. These findings indicate that mobile phone radiation can significantly impair spatial learning and reference memory and induce morphological changes in the hippocampal CA1 region.
基金Project supported by the National Natural Science Foundation of China(Grant No.61804055)"Chenguang Program"supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission,China(Grant No.17CG24)Shanghai Science and Technology Innovation Action Plan,China(Grant No.19JC1416700).
文摘The multiple ferroelectric polarization tuned by external electric field could be used to simulate the biological synaptic weight. Ferroelectric synaptic devices have two advantages compared with other reported ones: One is that the intrinsic switching of ferroelectric domains without invoking of defect migration as in resistive oxides, contributes reliable performance in these ferroelectric synapses. Another tremendous advantage is the extremely low energy consumption because the ferroelectric polarization is manipulated by electric field which eliminates the Joule heating by current as in magnetic and phase change memories. Ferroelectric synapses have potential for the construction of low-energy and effective brain-like intelligent networks. Here we summarize recent pioneering work of ferroelectric synapses involving the structure of ferroelectric tunnel junctions (FTJs), ferroelectric diodes (FDs), and ferroelectric field effect transistors (FeFETs), respectively, and shed light on future work needed to accelerate their application for efficient neural network.
文摘While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively,little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals.This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey,a model system for spinal injury research,in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site.Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials.They also showed the same activity-dependent depression over spike trains.However,regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude.For axons above the lesion site,the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals.However,in this case,there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains.Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery.However,the postsynaptic input was maintained at the unlesioned level using different synaptic properties.Conversely,the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger.This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs.The animal experiments were approved by the Animal Ethics Committee of Cambridge University.
基金This work was supported by grants from the National Natural Science Foundation of China(3147107,91132711,30970960)a Key Project of Shanghai Science and Technology Commission(15JC1400102,19ZR1416600).
文摘Neuronal oscillations in the hippocampus are critical for many brain functions including learning and memory.The underlying mechanism of oscillation generation has been extensively investigated in terms of chemical synapses and ion channels.Recently,electrical synapses have also been indicated to play important roles,as reported in various brain areas in vivo and in brain slices.However,this issue remains to be further clarified,including in hippocampal networks.Here,using the completely isolated hippocampus,we investigated in vitro the effect of electrical synapses on slow CA1 oscillations(0.5 Hz-1.5 Hz)generated intrinsically by the hippocampus.We found that these oscillations were totally abolished by bath application of a general blocker of gap junctions(carbenoxolone)or a specific blocker of electrical synapses(mefloquine),as determined by whole-cell recordings in both CA1 pyramidal cells and fast-spiking cells.Our findings indicate that electrical synapses are required for the hippocampal generation of slow CA1 oscillations.
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1A2C2004864)。
文摘Neuromorphic devices inspired by the human brain have attracted significant attention because of their excellent ability for cognitive and parallel computing.This study presents ZnO-based artificial synapses with peptide insulators for the electrical emulation of biological synapses.We demonstrated the dynamic responses of the device under various environmental conditions.The proton-conducting property of the tyrosine-rich peptide enables time-dependent responses under ambient conditions such that various aspects of synaptic behaviors are emulated by the devices.The transition from short-term memory to longterm memory is achieved via electrochemical doping of ZnO by protons.Furthermore,we demonstrate an image classification simulation using a multi-layer perceptron model to evaluate the potential of the device for use in neuromorphic computing.The neural network based on our device achieved a recognition accuracy of 87.47% for the MNIST handwritten digit images.This work proposes a novel device platform inspired by biosystems for brain-mimetic hardware systems.
