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Brain circuits for retching-like behavior

National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland laboratory (Guangzhou Regenerative Medicine and Health Guangdong laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University state key laboratory of cognitive neuroscience and learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Local field potentials,spiking activity,and receptive fields in human visual cortex

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Science China(Life Sciences) 2024年第3期67卷 543-554页

作者： Lu Luo Xiongfei Wang Junshi Lu Guanpeng Chen Guoming Luan Wu Li Qian Wang Fang Fang School of Psychological and cognitive Sciences and Beijing key laboratory of Behavior and Mental Health Peking UniversityBeijing 100871China School of Psychology Beijing Sport UniversityBeijing 100084China Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China Beijing key laboratory of Epilepsy Epilepsy CenterSanbo Brain HospitalCapital Medical UniversityBeijing 100093China IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China Beijing Institute for Brain Disorders Beijing 100069China state key laboratory of cognitive neuroscience and learning and IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing 100875China

The concept of receptive field(RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals,while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials(LFPs) and spiking activity in human visual cortex(V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from lowfrequency activity(LFA, 0.5–30 Hz) were larger than those estimated from low-gamma activity(LGA, 30–60 Hz) and high-gamma activity(HGA, 60–150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.

关键词： human visual cortex receptive field intracranial EEG local field potential spiking activity

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Reshaping the Cortical Connectivity Gradient by Long-Term cognitive Training During Development

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neuroscience Bulletin 2024年第1期40卷 50-64页

作者： Tianyong Xu Yunying Wu Yi Zhang Xi-Nian Zuo Feiyan Chen Changsong Zhou Bio-X laboratory School of PhysicsZhejiang UniversityHangzhou 310027China Qiushi Academy for Advanced Studies Zhejiang UniversityHangzhou 310027China state key laboratory of Modern Optical Instrumentation College of Optical Science and EngineeringZhejiang UniversityHangzhou 310027China state key laboratory of cognitive neuroscience and learning Bejing Normal UniversityBeijing 100875China Developmental Population neuroscience Research Center IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China Zhejiang Province key laboratory of Quantum Technology and Devices Zhejiang UniversityHangzhou 310027China Department of Physics Centre for Nonlinear Studies and Beijing-Hong Kong-Singapore Joint Centre for Nonlinear and Complex Systems(Hong Kong)Institute of Computational and Theoretical StudiesHong Kong Baptist UniversityHong Kong 999077China

The organization of the brain follows a topologi-cal hierarchy that changes dynamically during ***,it remains unknown whether and how cognitive training administered over multiple years during develop-ment can modify this hierarchical *** measuring the brain and behavior of school children who had carried out abacus-based mental calculation(AMC)training for five years(starting from 7 years to 12 years old)in pre-training and post-training,we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical *** observed the development-induced emergence of the default network,AMC training-promoted shifting,and regional changes in cortical ***,the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery *** found that gradient-based features can predict the math ability within *** findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.

关键词： Connectivity gradient cognitive training Development Neural plasticity Abacus-based mental calculation

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Shifts in intrinsic neural timescale of hippocampus support the maturation of inhibitory control and working memory in youth

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Medicine in Novel Technology and Devices 2024年第2期22卷 115-123页

作者： Debin Zeng Qiongling Li Deyu Li Shuyu Li Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science&Medical EngineeringBeihang UniversityBeijing100083China state key laboratory of cognitive neuroscience and learning Beijing Normal UniversityBeijing100875China Beijing key laboratory of Brain Imaging and Connectomics Beijing Normal UniversityBeijing100875China IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing100875China state key laboratory of Virtual Reaility technology and Systems Beihang UniversityBeijing100083China

The intrinsic neural timescale(INT)provides temporal windows in brain activity that process information of different durations,crucial for the integration and segregation of external inputs and ultimately shaping cognition and *** research has uncovered a pronounced INT hierarchy along the adult hippocampus's long***,the development of INT organization within the hippocampus—particularly the pattern of its hierarchical structure and its impact on cognitive development—has not been thoroughly investigated in ***,we discovered that the INT distribution in youth presents a distinct hierarchical structure along both posterioranterior and proximal-distal axes of the ***,this hierarchical structure correlates signifi-cantly with the first principal gradient of the hippocampal-cortical functional connectome and the thickness of hippocampal grey ***,we observed notable changes in the hippocampal INT landscape during youth,characterized by a general narrowing of timescales,alongside dedifferentiation along the hippocampal organizational *** maturational changes significantly link to improvements in inhibitory control and working memory ***,our findings reveal the developmental patterns of temporal integration and segregation hierarchies within hippocampus,and highlights the profound significance of INT as a neural underpinning that orchestrates cognitive growth.

关键词： Intrinsic neural timescale Hippocampus Development Inhibitory control and working memory

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Association between the frontoparietal network,clinical symptoms and treatment response in individuals with untreated anorexia nervosa

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General Psychiatry 2024年第3期37卷 364-374页

作者： Qianqian He Hui Zheng Jialin Zhang Ling Yue Qing Kang Cheng Lian Lei Guo Yan Chen Yanran Hu Yuping Wang Sufang Peng Zhen Wang Qiang Liu Jue Chen Department of Clinical Psychology Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Clinical Psychology Shanghai Pudong New Area Mental Health CenterTongji University School of MedicineShanghaiChina Shanghai key laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina state key laboratory of cognitive neuroscience and learning and IDG/McGovern Institute for Brain Research Bejing Normal UniversityBeijingChina

Background Anorexia nervosa(AN)has been characterised as a psychiatric disorder associated with increased ***,it remains difficult to predict treatment response in patients with *** cognitive abilities are known to be resistant to *** has been established that the frontoparietal control network(FPCN)is the direct counterpart of the executive control ***,the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in *** The study aimed to investigate the association between resting-state functional connectivity(RSFC)of the FPCN,clinical symptoms and treatment response in patients with *** In this case-control study,79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls(HCs)were recruited from January 2015 to March *** participants completed the Questionnaire Versionof the Eating Disorder Examination(version 6.0)to assess the severity of their eating disorder ***,RSFC data were obtained from all participants at baseline by functional magnetic resonance *** with AN underwent routine outpatient treatment at the 4th and 12th week,during which time their clinical symptoms were evaluated using the same measures as at *** Among the 79 patients,40 completed the 4-week follow-up and 35 completed the 12-week *** RSFC from the right posterior parietal cortex(PPC)and dorsolateral prefrontal cortex(diPFC)increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety *** multiple linear regression,the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image,after controlling for age,age of onset and body mass *** RSFC in the dIPFC to the middle temporal gyrus and the

关键词： symptoms routine prevention

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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC key laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan key lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK state key laboratory of cognitive neuroscience and learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China state key laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

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Neural Regeneration Research 2024年第3期19卷 657-662页

作者： Hang Yu Mingting Shao Xi Luo Chaoqin Pang Kwok-Fai So Jiandong Yu Li Zhang key laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina state key laboratory of Brain and cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina Department of Neurosurgery The First Affiliated Hospital of Bengbu Medical CollegeBengbuShandong ProvinceChina School of Psychology Shanghai University of SportShanghaiChina

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain *** regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains ***,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of *** assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical *** of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain *** summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

关键词： blood-brain barrier cognition hippocampus interneurons long-term potentiation microglial cell neuroinflammation spatial memory temporal epilepsy treadmill exercise

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Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei Qinghua Long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui Yang Xiaxia Zhang Ping Wang Zhanjun Zhang state key laboratory of cognitive neuroscience and learning&IDG/McGovern Institute for Brain Research Beijing Normal UniversityBeijing100875China Institute of Gerontology Hubei University of Chinese MedicineWuhan430065China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei University of Science and Technology XianningHubei437100China Institute of Brain and Psychological Science Sichuan Normal UniversityChengdu610066China key laboratory of Traditional Chinese Medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing key laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI Centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial ***,the specific associations between these pathological changes remain *** this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro *** investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular *** results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD ***,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic *** cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular *** intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and ***,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial *** conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

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STON2风险变异通过影响Syt1转运和突触功能导致精神分裂症样行为

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Science Bulletin 2024年第10期69卷 1458-1471页

作者：马远林高凯孙晓璇王金鑫杨扬武建荧柴安平姚立刘楠郁昊苏怡卢天兰王力芳岳伟华章晓辉徐林张岱李俊 Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Key Laboratory of Mental HealthChinese Academy of Medical SciencesBeijing 100191China The First Affiliated Hospital Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Changping laboratory Beijing 102206China d Chinese Institute for Brain Research Beijing 102206China laboratory of learning and Memory Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China Shenzhen key laboratory of Translational Research for Brain Diseases The Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China state key laboratory of cognitive neuroscience and learning IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China

Synaptic dysfunction is a core component of the pathophysiology of ***,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully *** Stonin 2(STON2)gene encodes a major adaptor for clathrin-mediated endocytosis(CME)of synaptic *** this study,we showed that the C-C(307Pro-851Ala)haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of *** found that schizophrenia-related STON2 variations led to protein dephosphorylation,which affected its interaction with synaptotagmin 1(Syt1),a calcium sensor protein located in the presynaptic membrane that is critical for ***2307Pro851Ala knockin mice exhibited deficits in synaptic transmission,short-term plasticity,and schizophrenia-like ***,among seven antipsychotic drugs,patients with the C-C(307Pro-851Ala)haplotype responded better to haloperidol than did the T-A(307Ser-851Ser)*** recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin *** findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME,which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

关键词： STON2 variations Schizophrenia Synaptic dysfunction Syt1 Haloperidol

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Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment

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neuroscience Bulletin 2023年第1期39卷 1-13页

作者： Ziwei Shang Junhao Huang Nan Liu Xiaohui Zhang state key laboratory of cognitive neuroscience and learning IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China

Differing from other subtypes of inhibitory interneuron,chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment(AIS)of targeted pyramidal cells(PCs).However,the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not *** realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs,we quantitatively demonstrate that the onset-timing of AIS-GABAergic input,relative to dendritic excitatory glutamatergic inputs,determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a *** specifically,AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+channels on summed synaptic excitation when they precede glutamatergic inputs by>15 ms,while for nearly concurrent excitatory inputs,they primarily produce a shunting inhibition at the ***,our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

关键词： GABAergic inputs Axon initial segment Synaptic integration Axo-axonic cell Chandelier cell NEURON simulation Dynamic clamp

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