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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

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

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

Microglia Suppresses Breast Cancer brain Metastasis via a Pro-inflammatory Response

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Neuroscience Bulletin 2024年第7期40卷 1034-1036页

作者： Shengbo Chen Yi-Jun Liu Department of Neurobiology of Affiliated Mental Health center and Hangzhou Seventh People's Hospital and School of brain science and brain Medicine 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 University1369 West Wenyi RoadHangzhou 311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou 310058China

Due to the obstacle of the blood-brain barrier(BBB)for drug delivery[1],breast cancer brain metastasis(BCBM)represents a worldwide health challenge with high *** BCBM formation and progression,brain metastases(BrMs)secret various factors,including cytokines and exosomes,and trigger the infiltration of tumours-associated macrophages(TAMs),which in turn become important components of brain tumour microenvironments(TME).

关键词： mortality tumour Breast

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

Progress and Implications from Genetic Studies of Bipolar Disorder

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Neuroscience Bulletin 2024年第8期40卷 1160-1172页

作者： Lingzhuo Kong Yiqing Chen Yuting Shen Danhua Zhang Chen Wei Jianbo Lai Shaohua Hu Department of Psychiatry the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China The Key Laboratory of Mental Disorder Management in Zhejiang Province Hangzhou310003China brain research Institute of Zhejiang University Hangzhou310003China Zhejiang Engineering center for Mathematical Mental Health Hangzhou310003China Department of Neurobiology NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brian Medicineand MOE Frontier Science Center for Brain Science and Brain-machine IntegrationZhejiang University School of MedicineHangzhou310003China

With the advancements in gene sequencing technologies,including genome-wide association studies,polygenetic risk scores,and high-throughput sequencing,there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder(BD).To date,intriguing genetic clues have been identified to explain the development of BD,as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic *** genes of BD,such as CACNA1C,ANK3,TRANK1,and CLOCK,have been found to be involved in various pathophysiological processes correlated with *** the specific roles of these genes have yet to be determined,genetic research on BD will help improve the prevention,therapeutics,and prognosis in clinical *** latest preclinical and clinical studies,and reviews of the genetics of BD,are analyzed in this review,aiming to summarize the progress in this intriguing field and to provide perspectives for individualized,precise,and effective clinical practice.

关键词： Bipolar disorder Genetics Risk gene Genome-wide association study Sequencing technology

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

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Identifying extracerebellar characteristics in a large cohort of 319 Chinese patients with spinocerebellar ataxia type 3

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中华医学杂志(英文版) 2024年第17期137卷 2131-2133页

作者： Li Donghui Yu Jinyang Zhu Chenhao Du Yichu Ma Yin Dong Yi Wu Zhiying Department of Medical Genetics and center for Rare Diseases and Department of Neurology in Second Affiliated Hospital and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation Zhejiang University School of Medicine Hangzhou Zhejiang China Nanhu brain-Computer Interface Institute Hangzhou Zhejiang China Department of Neurology Changxing People’s Hospital Changxing Zhejiang China moe frontier science center for brain science and brain-machine integration School of Brain Science and Brain Medicine Zhejiang University Hangzhou Zhejiang China

Chinese patients with adult onset leukodystrophy caused by CST3 variants

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Journal of Genetics and Genomics 2024年第7期51卷 778-780页

作者： Yi Zhang Zhi-Ying Wu Department of Medical Genetics and center for Rare Diseases Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical TranslationSecond Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu brain-computer Interface Institute HangzhouZhejiang 314050China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China moe frontier science center for brain science and brain-machine integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

Leukodystrophies represent a group of cerebral white matter disorders that mainly affect axon-glia *** disorders are clinically diverse and display significant genetic *** is challenging to differentiate hereditary leukodystrophies,particularly those that present in adulthood,from acquired leukodystrophies and other genetic disorders,such as multiple sclerosis(MS)or hereditary spastic paraplegia(HSP)(Wei et al.,2021).Over the past few decades,a series of causative genes associated with leukodystrophies have been identified(Kohler et al.,2018).Nevertheless,a significant proportion of patients still lack a precise molecular diagnosis.

关键词： al. patients Kohler