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Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal

Neuroscience Bulletin 2023年第5期39卷 731-744页

作者： Xiao-Wei Li Yi Ren Dong-Qing Shi Lei Qi Fang Xu Yanyang Xiao Pak-Ming Lau Guo-Qiang Bi CAS Key Laboratory of brain Function and Disease School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230027China CAS Key Laboratory of brain Connectome and Manipulation Interdisciplinary Center for Brain Informationthe Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China

Acetylcholine(ACh)is an important neuromod-ulator in various cognitive functions.However,it is unclear how ACh influences neural circuit dynamics by altering cellular properties.Here,we investigated how ACh influ-ences reverberatory activity in cultured neuronal networks.We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses,but to a much lesser extent at high doses.Moreover,high doses of ACh caused a longer duration of evoked reverberation,and a higher occur-rence of spontaneous activity.With whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal firing in a dose-dependent manner.Furthermore,all ACh-induced cellular and network changes were blocked by muscarinic,but not nicotinic receptor antagonists.With computational modeling,we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations.Thus,ACh modulates network dynamics in a biphasic fashion,probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

关键词： Acetylcholine Neuronal network Reverberation Synaptic current Excitability

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Mapping big brains at subcellular resolution in the era of big data in zoology

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Zoological Research 2022年第4期43卷 597-599页

作者： Yan Shen Lu-Feng Ding Chao-Yu Yang Fang Xu Pak-Ming Lau Guo-Qiang Bi Interdisciplinary Center for brain Information Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhenGuangdong 518000China division of Life sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230001China Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui 230001China

Connectome-scale structural mapping is fundamental for understanding the underlying mechanisms of brain cognition and brain disease pathogenesis.By combining rapidly developing three-dimensional(3D)imaging techniques and big data analysis methods,researchers are working on mesoscale mapping of mammalian brains at an accelerated pace.Here,we briefly describe existing brain-wide imaging strategies,especially our recently established primateoptimized pipeline capable of pan-brain neuronal connectivity mapping at subcellular resolution,and further discuss their vast application prospects in the big data era of zoology.

关键词： Mapping resolution mapping

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Conserved Spatiotemporal Dynamics with Millisecond Precision During Reverberatory Activity in a Self-organized Neuronal

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Neuroscience Bulletin 2023年第5期39卷 808-812页

作者： Dong-Qing Shi Fang Xu Guo-Qiang Bi Pak-Ming Lau division of Life sciences and Medicine University of Science and Technology of ChinaHefei 230026China Interdisciplinary Center for brain Information The BrainCognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Dear Editor,The timing of spiking activity across neurons is believed to play an important role in information coding in brain circuits1[1].At the cellular level,neurons can fire spikes with millisecond precision and the relative timing of pre-and postsynaptic spikes can determine the direction and extent of synaptic modification[2].When such spike-timing-dependent plasticity(STDP)and other physiological and anatomical properties are implemented in theoretical models,the simulated networks of interconnected spiking neurons exhibit neuronal groups with stereotypical time-locked spatiotemporal firing patterns with millisecond temporal precision[3].

关键词： second organized timing

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Fabrication of High-Density Out-of-Plane Microneedle Arrays with Various Heights and Diverse Cross-Sectional Shapes

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Nano-Micro Letters 2022年第2期14卷 60-78页

作者： Hyeonhee Roh Young Jun Yoon Jin Soo Park Dong-Hyun Kang Seung Min Kwak Byung Chul Lee Maesoon Im brain science Institute Korea Institute of Science and Technology(KIST)Seoul 02792South Korea division of Electrical Engineering College of EngineeringKorea UniversitySeoul 02841South Korea Micro/Nano Fabrication Center KISTSeoul 02792South Korea division of Bio‑Medical science&Technology KIST SchoolUniversity of Science&Technology(UST)Seoul 02792South Korea

Out-of-plane microneedle structures are widely used in various applications such as transcutaneous drug delivery and neural signal recording for brain machine interface.This work presents a novel but simple method to fabricate high-density silicon(Si)microneedle arrays with various heights and diverse cross-sectional shapes depending on photomask pattern designs.The proposed fabrication method is composed of a single photolithography and two subsequent deep reactive ion etching(DRIE)steps.First,a photoresist layer was patterned on a Si substrate to define areas to be etched,which will eventually determine the final location and shape of each individual microneedle.Then,the 1st DRIE step created deep trenches with a highly anisotropic etching of the Si substrate.Subsequently,the photoresist was removed for more isotropic etching;the 2nd DRIE isolated and sharpened microneedles from the predefined trench structures.Depending on diverse photomask designs,the 2nd DRIE formed arrays of microneedles that have various height distributions,as well as diverse cross-sectional shapes across the substrate.With these simple steps,high-aspect ratio microneedles were created in the high density of up to 625 microneedles mm^(-2)on a Si wafer.Insertion tests showed a small force as low as~172μN/microneedle is required for microneedle arrays to penetrate the dura mater of a mouse brain.To demonstrate a feasibility of drug delivery application,we also implemented silk microneedle arrays using molding processes.The fabrication method of the present study is expected to be broadly applicable to create microneedle structures for drug delivery,neuroprosthetic devices,and so on.

关键词： Microneedle Various heights Cross-sectional shapes Isotropic etch Deep reactive ion etching

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Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

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Neural Regeneration Research 2019年第6期14卷 1013-1024页

作者： Yang Wang De-Jun Bao Bin Xu Chuan-Dong Cheng Yong-Fei Dong Xiang-pin Wei Chao-Shi Niu Department of Neurosurgery First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China Anhui Medical University Auhui Province Medical Genetic Center Anhui Province Key Laboratory of brain Function and brain Disease

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage.Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral defi

关键词： nerve regeneration subarachnoid hemorrhage Wnt/Frizzled signaling pathway early brain injury nuclear factor-κB M2 type microglia peroxisome proliferator-activated receptor-γ inflammatory cytokines neural regeneration

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Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

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蛋白质与细胞:英文版 2023年第8期14卷 603-617页

作者： Min Wei Yanping Sun Shouzhen Li Yunuo Chen Longfei Li Minghao Fang Ronghua Shi Dali Tong Jutao Chen Yuqian Ma Kun Qu Mei Zhang Tian Xue division of Life sciences and Medicine Department of OphthalmologyThe First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230026China Hefei National Research Center for Physical sciences at the Microscale Neurodegenerative Disorder Research CenterCAS Key Laboratory of Brain Function and DiseaseUniversity of Science and Technology of ChinaHefei 230026China division of Life sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230026China Center for Excellence in brain science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100864China

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination.Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation.However,various types of neurons and glial cells exist in the retina,and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation.Therefore,we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice.The results demonstrated that,in addition to photoreceptors,other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation.Importantly,Müller glial cells(MGs)were identified as hub cells for intercellular interactions,displaying complex cell‒cell communication with other retinal cells.Furthermore,light increased the transcription of the deiodinase Dio2 in MGs,which converted thyroxine(T4)to active triiodothyronine(T3).Subsequently,light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions.As cones specifically express the thyroid hormone receptor Thrb,they responded to the increase in T3 by adjusting light responsiveness.Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones.These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

关键词： single cell Müller glial cells intercellular communication light/dark adaptation thyroid hormone signaling

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Form Properties of Moving Targets Bias Smooth Pursuit Target Selection in Monkeys

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神经科学通报:英文版 2023年第8期39卷 1246-1262页

作者： Huixi Dou Huan Wang Sainan Liu Jun Huang Zuxiang Liu Tiangang Zhou Yan Yang State Key Laboratory of brain and Cognitive science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Institute of Artifcial Intelligence Hefei Comprehensive National Science CenterHefei 230088China division of Life sciences and Medicine University of Science and Technology of ChinaHefei 230026China University of Chinese Academy of sciences Beijing 100049China

During natural viewing,we often recognize multiple objects,detect their motion,and select one object as the target to track.It remains to be determined how such behavior is guided by the integration of visual form and motion perception.To address this,we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task.We found that pursuit responses were biased toward the motion direction of a target with a hole.By computing the relative weighting,we found that the target with a hole exhibited a larger weight for vector computation.The global hole feature dominated other form properties.This dominance failed to account for changes in pursuit responses to a target with different forms moving singly.These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.

关键词： Global hole feature Smooth pursuit eye movements Sensorimotor transformation Visual form perception Visual motion perception Monkeys

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衰老和疾病相关的认知功能下降:表观遗传生物标志物及治疗靶点

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science Bulletin 2023年第16期68卷 1719-1721页

作者：张娟刘强 Department of Neurology The First Affiliated Hospital of USTCCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of ChinaHeifei 230027China Institute on Aging and brain Disorders The First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230027China Anhui Province Key Laboratory of Biomedical Aging Research University of Science and Technology of ChinaHefei 230027China CAS Key Laboratory of brain Function and Disease University of Science and Technology of ChinaHefei 230026China

Epigenetic mechanisms,including DNA methylation,histone modification,and non-coding RNAs(ncRNAs),have been widely implicated in synaptic plasticity,memory formation,and memory consolidation.Dysregulation in epigenetic mechanisms has been reported in aged brains as well as age-related diseases,such as Alzheimer’s disease(AD).The reversible nature of epigenetic changes and their role in regulating gene expression in response to environmental stimuli make them exciting targets for therapy.Here,we will briefly discuss epigenetic changes in aged and AD brains,epigenetic biomarkers for diagnosis and prognosis,as well as HDAC-based treatment regimes.

关键词： diagnosis 生物标志物 Alzheimer 表观遗传

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Antinociceptive effects of novel epibatidine analogs through activation of α4β2 nicotinic receptors

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science China(Life sciences) 2018年第6期61卷 688-695页

作者： Weiwei Li Jingyi Cai Benjamin H Wang Lanting Huang Jing Fan Yun Wang Institutes of brain science and State Key Laboratory of Medical Neurobiology Collaborative innovation Center for Brain Science Zhongshan Hospital Fudan University Shanghai 200032 China Department of Anesthesiology Shanghai Changzheng Hospital Second Military Medical University Shanghai 200003China east shanghai high school shanghai high school international division

The study of α4β2 nicotinic receptors has provided new indications in the treatment of pain. Efforts have been made to explore new α4β2 nicotinic receptor agonists, including TC-2559, as antinociceptive drugs. In this study, we discovered a set of novel epibatidine analogs with strong binding affinities to the α4β2 nicotinic receptors. Among these compounds, C-159, C-163, and C-9515 attenuated formalin-induced nociceptive responses in mice; C-9515 caused the most potent analgesic effect, which was blocked by mecamylamine, a non-selective nicotinic receptor antagonist. Furthermore, C-9515 potently inhibited chronic constriction injury(CCI)-induced neuropathic pain in rats, which was sensitive to DHβE, a selective α4β2 subtype antagonist,indicating that its analgesic effect was mediated by the activation of the α4β2 nicotinic receptors. In conclusion, the epibatidine analog C-9515 was found to be a potent α4β2 nicotinic receptor agonist with potent analgesic function, which demonstrated potential for the further exploration of its druggability.

关键词： epibatidine 类似物烟碱受体激活体收缩止痛剂有势力

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Computational neuroscience:a frontier of the 21st century

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National science Review 2020年第9期7卷 1418-1422页

作者： Xiao-Jing Wang Hailan Hu Chengcheng Huang Henry Kennedy Chengyu Tony Li Nikos Logothetis Zhong-Lin Lu Qingming Luo Mu-ming Poo Doris Tsao Si Wu Zhaohui Wu Xu Zhang Douglas Zhou division of Biology and Biological Engineering California Institute of Technology Howard Hughes Medical Institute School of Electronics Engineering and Computer science IDG/Mc Govern Institute for Brain Research PKU-Tsinghua Center for Life SciencesPeking University College of Computer science and Technology Zhejiang University Institute of brain-Intelligence science and Technology Zhangjiang Lab School of Mathematical sciences MOE-LSCand Institute of Natural Sciences Shanghai Jiao Tong University Center for Neural science New York University Center for Neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China School of Medicine Zhejiang University Department of Neuroscience and Department of Mathematics Center for the Neural Basis of Cognition University of Pittsburgh Université Claude Bernard Lyon 1 Inserm Stem Cell and Brain Research Institute U1208 Institute of Neuroscience State Key Laboratory of Neuroscience Chinese Academy of SciencesCAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Center for brain science and brain-Inspired Technology division of Arts and sciences and NYU-ECNU Institute of Cognitive Neuroscience NYU Shanghai School of Biomedical Engineering Hainan University Huazhong University of science and Technology-Suzhou Institute for brainsmatics

THEORY IN NEUROscience The human brain is a biological organ,weighing about three pounds or 1.4 kg,that determines our behaviors, thoughts,emotions and consciousness. Although comprising only 2%of the total body weigh... 详细信息

关键词： NETWORKS

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