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Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan Jia Gaogan Jia Luo Guo Nan Song Yu-Meng Wang Luoying Jiang Yilai Shu Yan Chen Shujia Zhu Huawei Li Wenyan Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China institutes of Biomedical sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200031China The institutes of brain science and the Collaborative Innovation Center for brain science Fudan UniversityShanghai 200032China Shanghai Center for brain science and brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

Versatile strategies for adult neurogenesis:avenues to repair the injured brain

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Neural Regeneration Research 2024年第4期19卷 774-780页

作者： Junyi Zhao Siyu Liu Xianyuan Xiang Xinzhou Zhu The brain Cognition and brain Disease Institute(BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences Faculty of Life and Health sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Shenzhen-Hong Kong Institute of brain science-Shenzhen Fundamental Research Institutions

brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

关键词： adult neurogenesis glia-to-neuron conversion ischemic stroke neurogenic niche neuroinflammation stem cell transplantation traumatic brain injury

The neuroscience of pain,addiction,and anesthesia

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Zoological Research 2024年第3期45卷 709-710页

作者： Ji Hu Ping Zheng School of Life science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Medical Neurobiology Institutes of Brain ScienceMOE Frontier Center for Brain ScienceDepartment of Neurology of Zhongshan HospitalFudan UniversityShanghai 200032China

Researchers and clinicians have long been interested in the mechanisms of pain,anesthesia,and addiction.The International Association for the Study of Pain(IASP)defines pain as an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage(Raja et al.,2020).Drug addiction refers to a condition of reliance that develops from regular drug consumption,which may lead to withdrawal symptoms when use is halted.Anesthesia involves the complete loss of consciousness induced by an inhaled or intravenous anesthetic(Tosello et al.,2022).In this special collection,Zoological Research presents research findings focused on pain,addiction,and anesthesia.

关键词： anesthesia damage

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of Life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of Life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences Department of Modern Life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of brain science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

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National science Review 2024年第4期11卷 70-83页

作者： Huiying Zhao Jinrong Liu Yujin Shao Xiang Feng Binhan Zhao Li Sun Yijun Liu Linghui Zeng Xiao-ming Li Hongbin Yang Shumin Duan Yan-qin Yu Department of Neurology of Second Affiliated Hospital and School of brain science and brain Medicine Zhejiang University School of Medicine Nanhu brain-Computer Interface Institute Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-Machine Integration State Key Laboratory of Brain-Machine Intelligence Zhejiang University NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine Hangzhou City University

The nucleus of Darkschewitsch(ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons(NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot shock.Optogenetic and chemogenetic manipulations revealed that NDGABA neurons mediate freezing behavior.Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray(l PAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part(Gi V). Together,these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the l PAG to Gi V, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

关键词： nucleus of Darkschewitsch GABAergic population defensive behavior freezing neural circuitry

Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of Medical sciences Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the School of Medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

Prompt learning in computer vision: a survey

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Frontiers of Information Technology & Electronic Engineering 2024年第1期25卷 42-63页

作者： Yiming LEI Jingqi LI Zilong LI Yuan CAO Hongming SHAN Shanghai Key Laboratory of Intelligent Information Processing School of Computer ScienceFudan UniversityShanghai 200438China Institute of science and Technology for brain-Inspired Intelligence Fudan UniversityShanghai 200433China MOE Frontiers Center for brain science Fudan UniversityShanghai 200433China Shanghai Center for brain science and brain-Inspired Technology Shanghai 201210China

Prompt learning has attracted broad attention in computer vision since the large pre-trained visionlanguagemodels (VLMs) exploded. Based on the close relationship between vision and language information builtby VLM, prompt learning becomes a crucial technique in many important applications such as artificial intelligencegenerated content (AIGC). In this survey, we provide a progressive and comprehensive review of visual promptlearning as related to AIGC. We begin by introducing VLM, the foundation of visual prompt learning. Then, wereview the vision prompt learning methods and prompt-guided generative models, and discuss how to improve theefficiency of adapting AIGC models to specific downstream tasks. Finally, we provide some promising researchdirections concerning prompt learning.

关键词： Prompt learning Visual prompt tuning(VPT) Image generation Image classification Artificial intelligence generated content(AIGC)

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang Department of Neurosurgery of Second Affiliated Hospital and School of brain science and brain Medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu brain-computer Interface Institute Hangzhou311100China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain unclear.Here,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was disrupted.Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm synapses.Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and density.Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

Structures and ion transport mechanisms of plant high-affinity potassium transporters

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Molecular Plant 2024年第3期17卷 409-422页

作者： Jiangqin Wang Yanping Luo Fan Ye Zhong Jie Ding Shao Jian Zheng Shuai Qiao Yong Wang Jiangtao Guo Wei Yang Nannan Su international institutes of Medicine the Fourth Affiliated HospitalZhejang University School of MedicineYiwuZhejiang 322000China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejang 310058China State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejang UniversityHangzhouZhejang 310058China College of Life sciences Zhejiang UniversityHangzhouZhejiang 310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Science and Brain-machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310058China Nanhu brain-computer Interface Institute Hangzhou.Zheiang 311100.China

Plant high-affinity K^(+) transporters(HKTs)mediate Na^(+) and K^(+) uptake,maintain Na^(+)/K^(+) homeostasis,and therefore play crucial roles in plant salt tolerance.In this study,we present cryoelectron microscopy structures of HKTs from two classes,classI HKT1;1 from Arabidopsis thaliana(AtHKT1;1)and class II HKT2;1 from Triticum aestivum(TaHKT2;1),in both Na^(+) -and K^(+) -bound states at 2.6-to 3.0-A resolutions.BothAtHKT1;1and TaHKT2;1function ashomodimers.Each HKT subunit consists of four tan-dem domain units(D1-D4)with a repeated K^(+) -channel-like M-P-M topology.In each subunit,D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry.Although both TaHKT2;1and AtHKT1;1 have only one putative Na^(+) ion bound in the selectivity filter with a similar coordination pattern,the two HKTs display different K^(+) binding modes in the filter.TaHKT2;1 has three K^(+) ions bound in the selec-tivity filter,but AtHKT1;1 has only two K^(+) ions bound in the filter,which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif.These structures,along with compu-tational,mutational,and electrophysiological analyses,enable us to pinpoint key residues that are critical for the ion selectivity of HKTs.The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

关键词： HKTs structure ion selectivity mechanism salt tolerance