The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to develop artificial visual synapses that integrate optical sensing and synaptic functions.This study fully leverages the excellent photoresponsivity proper-ties of the PM6:Y6 system to construct a vertical photo-tunable organic memristor and conducts in-depth research on its resis-tive switching performance,photodetection capability,and simulation of photo-synaptic behavior,showcasing its excellent per-formance in processing visual information and simulating neuromorphic behaviors.The device achieves stable and gradual resis-tance change,successfully simulating voltage-controlled long-term potentiation/depression(LTP/LTD),and exhibits various photo-electric synergistic regulation of synaptic plasticity.Moreover,the device has successfully simulated the image percep-tion and recognition functions of the human visual nervous system.The non-volatile Au/PM6:Y6/ITO memristor is used as an artificial synapse and neuron modeling,building a hierarchical coordinated processing SLP-CNN cascade neural network for visual image recognition training,its linear tunable photoconductivity characteristic serves as the weight update of the net-work,achieving a recognition accuracy of up to 93.4%.Compared with the single-layer visual target recognition model,this scheme has improved the recognition accuracy by 19.2%.
To emulate the functionality of the human retina and achieve a neuromorphic visual system,the development of a photonic synapse capable of multispectral color discrimination is of paramount importance.However,attaining robust color discrimination across a wide intensity range,even irrespective of medium limitations in the channel layer,poses a significant challenge.Here,we propose an approach that can bestow the color-discriminating synaptic functionality upon a three-terminal transistor flash memory even with enhanced discriminating capabilities.By incorporating the strong induced dipole moment effect at the excitation,modulated by the wavelength of the incident light,into the floating gate,we achieve outstanding RGB color-discriminating synaptic functionality within a remarkable intensity range spanning from 0.05 to 40 mW cm^(-2).This approach is not restricted to a specific medium in the channel layer,thereby enhancing its applicability.The effectiveness of this color-discriminating synaptic functionality is demonstrated through visual pre-processing of a photonic synapse array,involving the differentiation of RGB channels and the enhancement of image contrast with noise reduction.Consequently,a convolutional neural network can achieve an impressive inference accuracy of over 94%for Canadian-Institute-For-Advanced-Research-10 colorful image recognition task after the pre-processing.Our proposed approach offers a promising solution for achieving robust and versatile RGB color discrimination in photonic synapses,enabling significant advancements in artificial visual systems.
Bum Ho JeongJaewon LeeMiju KuJongmin LeeDohyung KimSeokhyun HamKyu-Tae LeeYoung-Beom KimHui Joon Park
Dementia is characterized by synaptic and neuronal dysfunction in disease-specific brain regions.Repeated failure of dementia clinical trials with therapeutic drugs targeting abnormal protein aggregates has caused researchers to shift their focus to synaptic functions and increased the importance of clinically available imaging for synaptic density and the development of synapse-targeted intervention.Synaptic density imaging with positron emission tomography(PET)tracer enables non-invasive detection of synaptic loss and hence investigates the association with other neuropathological events exemplified by disease-specific abnormal protein accumulation.Many studies have reviewed the progress of synaptic density imaging;however,to our knowledge,there is no article yet that summarizes the research progress of multimodal imaging of synaptic density tracers combined with other dementia biomarkers.Moreover,synaptic function intervention for dementia therapy has not yet been summarized.In this review,first we detail the progress of synaptic density imaging including tracer development and preclinical/clinical application,followed by a discussion of multimodal imaging of synaptic density tracers combined with classic dementia biomarkers in the clinical research stage.Finally,we briefly summarize the synapse-targeted drugs for dementia therapy.
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal o
Dear Editor,SARS-CoV-2 is the virus that caused the COVID-19 pandemic,leading to more than 774 million cases and 7,037,007 deaths by March 2024(World Health Organization,http://covid19.who.int/).Despite effective treatments,15%-20%of patients experience long-term symptoms,such as breathlessness,fatigue,depression,and cognitive impairment,which are often linked to an excessive immune response[1].All variants of the virus(α,,,Omicron,and BA.1),which can potentially access the brain via the olfactory mucosa,have been found in the brains of Syrian hamsters,triggering inflammation and demonstrating axonal travel[2].
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate targets.Although several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after injury.Herein,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.
Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic s
