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Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice

Neuroscience Bulletin 2023年第1期39卷 29-40页

作者： Xiaoke Xie Shangyue Gong Ning Sun Jiazhu Zhu Xiaobin Xu Yongxian Xu Xiaojing Li Zhenhong Du Xuanting Liu Jianmin Zhang Wei Gong Ke Si department of Psychiatry The First Affiliated HospitalZhejiang University School of MedicineHangzhou310012China College of Biomedical Engineering and Instrument science Zhejiang UniversityHangzhou310012China Intelligent Optics&Photonics Research Center Jiaxing Research InstituteZhejiang UniversityJiaxing314001China department of Neurosurgery of the second affiliated hospital Zhejiang University School of MedicineHangzhou310012China MOE Frontier science Center for brain science&brain-Machine Integration NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310012China State Key Laboratory of Modern Optical Instrumentation College of Optical Science and EngineeringZhejiang UniversityHangzhou310012China

Fear memory contextualization is critical for selecting adaptive behavior to *** fear conditioning(CFC)is a classical model for elucidating related underlying neuronal *** primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly ***,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in *** frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve *** to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)*** findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.

关键词： Contextual fear conditioning Calcium imaging Primary visual cortex Cortical plasticity Microglial depletion Learning and memory

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Rapid Eye Movement Sleep Consolidates Social Memory

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Neuroscience Bulletin 2023年第10期39卷 1598-1600页

作者： Jingkai Fan Fang Zhou Junqiang Zheng Han Xu department of neurobiology and department of neurology of the second Afliated hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-Machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou 311121China NHC and CAMS Key Laboratory of Medical neurobiology Zhejiang UniversityHangzhou 310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China

Social memory is one of declarative memory which is essential for animals to exhibit appropriate social *** suggests that the hippocampus,particularly the CA2 region,plays an important role in encoding and consolidating social memory[1].Rapid eye movement(REM)sleep has been suggested to contribute to social memory consolidation by up-regulating synaptic plasticity,local field potentials,and dendritic activity[2].

关键词： memory plasticity consolidation

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The Pathology of Primary Familial brain Calcification:Implications for Treatment

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Neuroscience Bulletin 2023年第4期39卷 659-674页

作者： Xuan Xu Hao Sun Junyu Luo Xuewen Cheng Wenqi Lv Wei Luo Wan-Jin Chen Zhi-Qi Xiong Jing-Yu Liu Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai200031China College of Life science and Technology Huazhong University of Science and TechnologyWuhan430074China department of neurology and Institute of neurology of First affiliated hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhou350005China department of neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China

Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and ***,the etiology of PFBC is largely unknown,and no specific prevention or treatment is *** the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in *** this review,considering mechanistic studies of these genes at the cellular level and in animals,we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC *** systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.

关键词： Primary familial brain calcification Causative gene Pathogenesis Preventive and therapeutic strategy

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A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior

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Neuroscience Bulletin 2022年第6期38卷 565-575页

作者： Di Zheng Jja-Yu Fu Meng-Yu Tang iao-Dan Yu Yi Zhu Chen Jie Shen Chun-Yue Li Shi-Ze Xiel Shan Lin Minmin Luo Xiao-Ming Li department of neurobiology and department of neurology of Second Affliated HospitalZhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical neurobiology MOE Frontier Science Center for Brain Research and Brainmachine IntegrationSchool of Brain Science and Brian MedicineZhejiang UniversityHangzhou 310058China National Institute of Biological sciences(NIBS) Bejing 102206China Chinese Institute for brain Research Beijing 102206China school of Life sciences Tsinghua UniversityBejing 100084China Center for brain science and brain-Inspired Intelligence Research Units for Emotion and Emotion DisordersChinese Academy of Medical SciencesChina/Guangdong-Hong Kong-Macao Greater Bay AreaJoint Institute for Genetics and Genome Medicine Between Zhejiang University and University of TorontoHangzhou 310058.China

Licking behavior is important for water *** deep mesencephalic nucleus(DpMe)has been implicated in instinctive ***,whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains ***,we found that the activity of the DpMe decreased during water *** of vesicular glutamate transporter 2-positive(VGLUT2+)neurons in the DpMe resulted in increased water ***-expressing(SST+),but not protein kinase C-expressing(PKC-8+),GABAergic neurons in the central amygdala(CeA)preferentially innervated DpMe VGLUT2+*** SST+neurons in the CeA projecting to the DpMe were activated at the onset of licking *** of these CeA SST+GABAergic neurons,but not PKC-8+GABAergic neurons,projecting to the DpMe was sufficient to induce licking behavior and promote water *** findings redefine the roles of the DpMe and reveal a novel CeAssT_DpMevcLUT?cireuit that regulaes icking behavior and promotes water intake.

关键词： Midbrain Amygdala Licking Neural Circuit Optogenetics

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Transient neurogenesis in ischemic cortex from Sox2^(+)astrocytes

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Neural Regeneration Research 2023年第7期18卷 1521-1526页

作者： Jia-Lei Yang Hong Fan Fan-Fan Fu Bao-Lin Guo Ying Huang Li Sun Wen-Ting Wang Jun-Ling Xing Xin-Tian Hu Yu-Qiang Ding Kun Zhang Ying-Zhou Hu Ya-Zhou Wang department of neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina China National Clinical Research Center for Neurological Diseases Department of NeurologyBeijing Tiantan HospitalBeijingChina department of neurology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina State Key Laboratory of Medical neurobiology and MOE Frontiers Center for brain science Institute of Brain ScienceFudan UniversityShanghaiChina Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan ProvinceChina

The adult cortex has long been regarded as *** injury can induce neurogenesis in the adult cortex is still ***,we report that focal ischemia stimulates a transient wave of local *** 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ***-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem *** a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new ***,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult *** addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca *** findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.

关键词： adult astrocyte cortex fate-mapping ischemia local neurogenesis neural stem cells Sox2

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Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1154-1160页

作者： Ting Shen Jia-Li Pu Ya-Si Jiang Yu-Mei Yue Ting-Ting He Bo-Yi Qu Shuai Zhao Ya-Ping Yan Hsin-Yi Lai Bao-Rong Zhang department of neurology of the second affiliated hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of neurology of the second affiliated hospital Interdisciplinary Institute of Neuroscience and TechnologyKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang ProvinceChina department of neurology of Sir Run Run Shaw hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina College of Biomedical Engineering and Instrument science Key Laboratory for Biomedical Engineering of Ministry of EducationZhejiang UniversityHangzhouZhejiang ProvinceChina

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors

关键词： cognition imaging genetics magnetic resonance imaging multi-modality Parkinson’s disease polygenic risk score single nucleotide polymorphism ultra-high field

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Hunting out the repeat expansion in Huntington's pigs

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Protein & Cell 2023年第12期14卷 871-873页

作者： Guang Yang Boxun Lu neurology department at Huashan hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200438China

A recent study from Yan et al.(2023)provides the milestone evidence in the large animal model demonstrating genome editing as a potential therapeutic strategy for Huntington's disease treatment.

关键词： treatment. Huntington expansion

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Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson’s Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress

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Chinese Journal of Integrative medicine 2023年第1期29卷 19-27页

作者： LI Yan-rong FAN Hui-jie SUN Rui-rui JIA Lu YANG Li-yang ZHANG Hai-fei JIN Xiao-ming XIAO Bao-guo MA Cun-gen CHAI Zhi The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese medicine Shanxi University of Chinese MedicineJinzhongShanxi Province030619China Institute of brain science department Neurology of First Affiliated HospitalShanxi Datong UniversityDatongShanxi Province037009China department of Anatomy and Cell Biology Department of Neurological SurgerySpinal Cord and Brain Injury Research GroupStark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisIN46202USA Institute of neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghai200025China

Objective:To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill(WYP) on Parkinson’s disease(PD) model ***:Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal,PD,and PD+WYP groups,12 mice in each *** week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) was used to establish the classical PD model in ***,mice in the PD+WYP group were administrated with 16 g/kg WYP,twice daily by *** 14 days of administration,gait test,open field test and pole test were measured to evaluate the movement *** hydroxylase(TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein(GRP78) in striatum and cortex were observed by *** levels of TH,GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,ATF6,CHOP,ASK1,p-JNK,Caspase-12,-9 and-3 in brain were detected by Western ***:Compared with the PD group,WYP treatment ameliorated gait balance ability in PD mice(P<0.05).Similarly,WYP increased the total distance and average speed(P<0.05or P<0.01),reduced rest time and pole time(P<0.05).Moreover,WYP significantly increased TH positive cells(P<0.01).Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and ***,WYP treatment significantly decreased the protein expressions of GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,CHOP,Caspase-12 and Caspase-9(P<0.05or P<0.01).Conclusions:WYP ameliorated motor symptoms and pathological lesion of PD mice,which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

关键词： Wuzi Yanzong Pill Parkinson’s disease dopaminergic neurons endoplasmic reticulum stress apoptosis

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Latest innovations in the treatment of Wilson's disease

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iLIVER 2022年第3期1卷 181-186页

作者： Zi-Wei Zheng Yi Dong Zhi-Ying Wu department of neurology and department of Medical Genetics in second affiliated hospital And Key Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouChina

Wilson's disease(WD),also called hepatolenticular degeneration,is an autosomal recessive copper dysfunction disorder that is among the few treatable neurogenetic *** main goals for controlling WD are to lower copper intake and encourage copper *** treatments and low-copper diets are available,but many problems *** example,the current treatments cannot fix copper metabolism and are unable to cross the blood-brain ***,severe side effects have been experienced by many patients with *** lifelong therapy is required for this disease,adherence to medical therapy and best practices for monitoring and personalizing therapy continue to evolve;some of these issues are being addressed in ongoing ***,novel chelating agents,gene therapies using adeno-associated viruses,and variant-specific therapies that may improve neurological outcomes are in ***,we review the latest treatment innovations that may play an essential role for patients with WD in the future.

关键词： Wilson's disease Treatment Innovation ATP7B

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CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain

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Neuroscience Bulletin 2023年第6期39卷 947-961页

作者： Ting Xu Zhen-Yu Li Meng Liu Su-Bo Zhang Huan-Huan Ding Jia-Yan Wu Su-Yan Lin Jun Liu Jia-You Wei Xue-Qin Zhang Wen-Jun Xin Neuroscience Program of Zhongshan school of medicine and the Fifth affiliated hospital Sun Yat-sen UniversityGuangzhou510080China Guangdong Province Key Laboratory of brain Function and Disease Sun Yat-sen UniversityGuangzhou510120China department of Anesthesia and Pain medicine Guangzhou First People’s HospitalGuangzhou510000China department of Physiology Xuzhou Medical UniversityXuzhou221004China department of neurology The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou510000China Guangdong Provincial Engineering Research Center of Molecular Imaging Guangdong Provincial Key Laboratory of Biomedical Imagingand Department of Interventional MedicineThe Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai519000China The affiliated brain hospital(Guangzhou Huiai hospital)and school of Health Management Guangzhou Medical UniversityGuangzhou510182China Guangdong-Hong Kong-Macao Greater Bay Area Center for brain science and brain-Inspired Intelligence Guangzhou510000China

Effective treatments for neuropathic pain are lacking due to our limited understanding of the *** circRNAs are mainly enriched in the central nervous ***,their function in various physiological and pathological conditions have yet to be ***,we identified circFhit,an exon-intron circRNA expressed in GABAergic neurons,which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic ***,we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R^(+) neurons by promoting the expression of its parental gene Fhit in ***,circFhit was directly bound to the intronic region of Fhit,and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit *** summary,we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R^(+) neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

关键词： Chronic pain Neuropathic pain CircRNA Inhibitory transmission Epigenetic regulation

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