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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 *** and chemogenetic manipulations revealed that NDGABA neurons mediate freezing ***, 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

Meta Shack–Hartmannwavefront sensor with large sampling density and large angular field of view:phase imaging of complex objects

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Light(Science & Applications) 2024年第9期13卷 1908-1918页

作者： Gi-Hyun Go Dong-gu Lee Jaeyeon Oh Gookho Song Doeon Lee Mooseok Jang department of Bio and brain Engineering Korea Advanced Institute of Science and Technology(KAIST)DaejeonRepublic of Korea

Shack–Hartmann wavefront sensors measure the local slopes of an incoming wavefront based on the displacement of focal spots created by a lenslet array,serving as key components for adaptive optics for astronomical and biomedical ***,the challenges in increasing the density and the curvature of the lenslet have limited the use of such wavefront sensors in characterizing slowly varying wavefront ***,we develop a metasurfaceenhanced Shack–Hartmann wavefront sensor(meta SHWFS)to break this limit,considering the interplay between the lenslet parameters and the performance of *** experimentally validate the meta SHWFS with a sampling density of 5963 permm2 and a maximum acceptance angle of 8°which outperforms the traditional SFWFS by an order of ***,to the best of our knowledge,we demonstrate the first use of a wavefront sensing scheme in single-shot phase imaging of highly complex patterns,including biological tissue *** proposed approach opens up new opportunities in incorporating exceptional light manipulation capabilities of the metasurface platform in complex wavefront characterization.

关键词： angular curvature exceptional

Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

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Journal of Genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin Fu Yu-Lan Chen Hong-Fu Li Zhi-Ying Wu Dian-Fu Chen department of Medical Genetics and Center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science Center for brain Science and brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period

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Protein & Cell 2024年第1期15卷 21-35页

作者： Zhenmeiyu Li Guoping Liu Lin Yang Mengge Sun Zhuangzhi Zhang Zhejun Xu Yanjing Gao Xin Jiang Zihao Su Xiaosu Li Zhengang Yang State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for brain Science Institutes of Brain Scienceand Department of NeurologyZhongshan HospitalFudan UniversityShanghai 200433China

The seat of human intelligence is the human cerebral cortex,which is responsible for our exceptional cognitive *** principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so *** remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells,primary neural stem cells in the cortex,generate cortical pyramidal neurons for more than 130 days,whereas the same process takes only about 7 days in *** molecular mechanisms underlying this difference are largely ***,we found that bone morphogenic protein 7(BMP7)is expressed by increasing the number of corti-cal radial glial cells during mammalian evolution(mouse,ferret,monkey,and human).BMP7 expression in cortical radial glial cells promotes neurogenesis,inhibits gliogenesis,and thereby increases the length of the neurogenic period,whereas Sonic Hedgehog(SHH)signaling promotes cortical *** demonstrate that BMP7 sign-aling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor *** propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.

关键词： radial glia cortical neurogenesis cortical gliogenesis cortical evolution BMP7 SHH

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration Research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of brain and Cognitive Neuroscience Guilin Medical University department of Genetic Disease Research Osaka Metropolitan University Graduate School of Medicine department of Scientific Research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,*** works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s *** intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent ***,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical ***,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in *** the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent *** findings indicate strong cross-talk between the two proteins in physiology and *** this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

Neural Circuitry Involving Substance P in Male Sexual Behavior

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Neuroscience Bulletin 2024年第4期40卷 544-546页

作者： Xinrong Wang Junqiang Zheng Han Xu department of Neurobiology and department of Neurology of the Second Affiliated Hospital and School of brain Science and brain Medicine Zhejiang University School of MedicineHangzhou310058China Nanhu brain-Computer Interface Institute Hangzhou311100China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

Male sexual behavior is an innate social behavior crucial for reproduction[1].Previous studies have identified several brain regions crucial for the control of both sexual and aggressive behaviors in ***,molecularly specified neural circuits that specifically control male sexual behavior remain *** with the inherently rewarding nature of sexual behavior,previous research has implicated the role of the dopamine system in regulating sexual desire[2].However,the interaction between reward and copulation at the circuit level remains largely ***,it is unclear if the associated neural pathways are specific in modulating sexual reward.

关键词： behavior neural specified

Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions

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Neural Regeneration Research 2024年第9期19卷 1973-1980页

作者： Yumei Yue Xiaodan Zhang Wen Lv Hsin-Yi Lai Ting Shen department of Neurology of Sir Run Run Shaw Hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of Emergency Medicine The University of Hong KongHong Kong Special Administrative RegionChina department of Neurology of the Second Affiliated Hospital and School of brain Science and brain Medicine Interdisciplinary Institute of Neuroscience and TechnologyKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang ProvinceChina College of Biomedical Engineering and Instrument Science Zhejiang UniversityHangzhouZhejiang ProvinceChina MOE Frontier Science Center for brain Science and brain-Machine Integration State Key Laboratory of Brain-machine IntelligenceSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina

Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic *** parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related *** glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial *** of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal ***,impairment of the glymphatic system could be considered as the final common pathway to *** evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions *** review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related *** focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and *** review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

关键词： atypical parkinsonism glymphatic system magnetic resonance imaging neurotoxic proteins Parkinson’s disease

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 ***,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 *** 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 *** synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and *** 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

Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations