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Region-specific role of DNA methylation in the consolidation and reconsolidation of appetitive memories associated with morphine in rats

Region-specific role of DNA methylation in the consolidation...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jian-Jun Zhang Peng Liu Nan Sui Key Laboratory of Mental Health Institute of PsychologyChinese Academy of Science Institute of Psychology University of Chinese Academy of Science

Objective Recent studies indicated epigenetic modification, especially DNA methylation, play an important role in the synaptic plasticity and fear memory. However, it is not clear whether DNA methylation is involved in opiate addiction. Methods In this study, using the morphine-induced conditioned place preference(m CPP) model in rats, we injected 5-aza-2-deoxycytidine(5-aza), a DNA methyltransferases(DNMTs) inhibitor, into hippocampus(CA1) and medial prefrontal cortex(m PFC) to determine the role of DNA methylation in the consolidation of morphine-related memory. Moreover, we injected 5-aza into basolateral amygdala(BLA), central nucleus of amygdala(Ce A), nucleus accumbens(NAc) shell and core to explore the effects of DNA methylation on the reconsolidation. Results(1) 5-aza injection into CA1 but not into m PFC significantly attenuated the consolidation of m CPP.(2) 5-aza injection into BLA but not Ce A, NAc shell or core inhibited the reconsolidation of m CPP. Conclusion These results indicate that the consolidation and reconsolidation of drug-related memory are region-spcific regulated by DNA methylation.

关键词： DNA methylation morphine conditioned place preference hippocampus prelimbic cortex basolateral amygdala

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Quantitative analysis of vesicle recycling at the calyx of Held synapse

Quantitative analysis of vesicle recycling at the calyx of H...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Qianwen Zhu Xufeng Qiu Jianyuan Sun State Key Laboratory of Brain and Cognitive Sciences Institute of BiophysicsChinese Academy of Sciences University of Chinese Academy of Sciences Center of Parkinson's Disease Beijing Institute for Brain Disorders

Vesicle recycling is pivotal for maintaining reliable synaptic signaling, but its basic properties remain poorly understood. Here, we developed an approach to quantitatively analyze the kinetics of vesicle recycling with exquisite signal and temporal resolution at the calyx of Held synapse. The combination of this novel electrophysiological approach with electron microscopy revealed that 0% of vesicles（70,000 out of 30,000） in the nerve terminal are involved in recycling. Under sustained stimulation, recycled vesicles start to be reused in tens of seconds when 7% of the preserved vesicles in the recycling pool（RP） are depleted. The heterogeneity of vesicle recycling as well as two kinetic components of RP depletion revealed the existence of a replenishable pool of vesicles prior to the priming stage and led to a realistic kinetic model that assesses the size of the sub-pools of the RP. Thus, our study quantified the kinetics of vesicle recycling and kinetically dissected the whole vesicle pool in the calyceal terminal into the readily-releasable pool（.6%）, the readily-priming pool（6%）, the pre-mature pool（3%） and the resting pool（0%）.

关键词： kinetics vesicle recycling vesicle pool calyx of Held short-term plasticity

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How does the CA1 neuron integrate synaptic inputs?

How does the CA1 neuron integrate synaptic inputs?

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Songting Li Nan Liu Xiao-hui Zhang Douglas Zhou David Cai Department of Mathematics MOE-LSC and Institute of Natural SciencesShanghai Jiao Tong University Courant Institute of Mathematical Sciences and Center for Neural Science New York University State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research Beijing Normal University NYUAD Institute New York University Abu Dhabi

A neuron receives thousands of synaptic inputs from its dendrite and integrates them to process information. Many experimental results demonstrate the dendritic integration could be highly nonlinear, yet few theoretical analyses have been performed to obtain a precise quantitative characterization analytically. Based on asymptotic analysis of a passive cable model, we derive a bilinear spatiotemporal dendritic integration rule for a pair of time-dependent synaptic inputs. Surprisingly, the above rule, which is obtained from idealized models, can be verified both in simulations of a realistic CA1 pyramidal neuron modeling and in electrophysiological experiments of rat hippocampal CA1 neurons. Our results demonstrate that the integration of multiple synaptic inputs for CA1 neurons can be decomposed into the sum of all possible pairwise integration with each paired integration obeying a bilinear rule.

关键词： Synaptic inputs dendritic integration bilinear rule CA1 pyramidal neuron

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CHD2 is Required for Embryonic Neurogenesis in the Developing Cerebral Cortex

CHD2 is Required for Embryonic Neurogenesis in the Developin...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Tianjin shen Fen Ji Jianwei Jiao State Key Laboratory of Reproductive Biology Institute of ZoologyChinese Academy of Sciences

Chromodomain helicase DNA-binding protein 2(CHD2) has been associated with a broad spectrum of neurodevelopmental disorders, such as autism spectrum disorders and intellectual disability. However, it is largely unknown whether and how CHD2 is involved in brain development. Here, we demonstrate that CHD2 is predominantly expressed in Pax61 radial glial cells(RGs) but rarely expressed in Tbr21 intermediate progenitors(IPs). Importantly, the suppression of CHD2 expression inhibits the self-renewal of RGs and increases the generation of IPs and the production of neurons. CHD2 mediates these functions by directly binding to the genomic region of repressor element 1-silencing transcription factor(REST), thereby regulating the expression of REST. Furthermore, the overexpression of REST rescues the defect in neurogenesis caused by CHD2 knockdown. Taken together, these findings demonstrate an essential role of CHD2 in the maintenance of the RGs self-renewal levels, the subsequent generation of IPs, and neuronal output during neurogenesis in cerebral cortical development, suggesting that inactivation of CHD2 during neurogenesis might contribute to abnormal neurodevelopment.

关键词： Neural stem cell differentiation proliferation brain development neurogenesis

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Neurexin restricts L4 columnar targeting through modulating Ephrin clustering

Neurexin restricts L4 columnar targeting through modulating ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yao Tian Lina Liu Wei Xie Junhai Han Institute of Life Sciences the Key Laboratory of Developmental Genes and Human DiseaseSoutheast University Co-innovation Center of Neuroregeneration Nantong University

Columnar restriction is commonly observed in vertebrates and invertebrate nerve system, which helps to form non-overlapping receptive fields and preserve the spatial sensory information from the periphery. Columnar restriction is thought to be mediated by contact-dependent repulsive interactions that are regulated by cell surface proteins. Neurexins are cell adhesion molecules involved in synapse formation and synaptic transmission. However, the potential roles of Neurexin in neural early development are unclear. Here, we showed that Neurexin is accumulated in the growth cones of lamina neurons in the Drosophila visual system. Depletion of Neurexin results in L4 axons project into neighboring columns. We revealed that Neurexin interacts with Ephrin and L4-expressed Ephrin is essential for their axons restricting in columns. Finally, we demonstrated that Neurexin-Ephrin interaction facilitates Ephrin clustering and stability. Our study demonstrates that Neurexin mediates columnar restriction through modulating Ephrin clustering and stability, and this work supports a model in which L4-expressed Ephrin restricts their axons in columns.

关键词： neurexin Ephrin axon targeting/axonal restriction Drosophila visual system

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Fear Erasure Facilitated by Inhibitory Neuron Transplantation

Fear Erasure Facilitated by Inhibitory Neuron Transplantatio...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Wu-Zhou Yang Xuan-Fu Chen Xiao Liu Min Wang Xin Su Bin-Long Qiu Wen-Xiang Hu Lin-Yun Liu Yong-Chun Yu Institute of Neurobiology Institute of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University School of Life Sciences Fudan University State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences

Although extinction training or drug treatment are effective in reducing bad memory such as post-traumatic stress disorder(PTSD), the inappropriate fear memories are resistant to erasure. Here, we show that transplanted immature interneuron can functionally integrate into the host amygdala circuits. We found inhibitory neuron transplantation do not alter host fear memory formation. However, after extinction training, host mice exhibited a marked reduction of spontaneous recovery and context-dependent renewal. Interestingly, only approximately two weeks after transplantation, fear extinction training produces enduring attenuation of fear response. Further studies revealed that transplanted interneurons promote long-term synaptic plasticity and modulate excitatory-inhibitory balance. Taken together, our findings suggest that interneuron transplantation could modify neural circuits in amygdala and provide a novel strategy in preventing extinction-resistant pathological fear.

关键词： Fear interneurons transplatation

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Spatiotemporal Dynamics and Regulation of Multiple Contraction Centers in Migratory Neurons

Spatiotemporal Dynamics and Regulation of Multiple Contracti...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jian Jiang Zheng-hong Zhang Xiao-bin Yuan Mu-ming Poo Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain ScienceShanghai Institutes for Biological SciencesChinese Academy of Sciences Graduate School of the Chinese Academy of Sciences

Traction force against the substrate is required for neuronal migration, but how it is generated and regulated remains controversial. Using traction force microscopy, we showed in cultured granule cells the coexistence of three distinct contraction centers(CCs) that are located at the distal and proximal regions of the leading process as well as at the trailing process, regions exhibiting high-level myosin-II activities. The activities of CCs depended on myosin-II, actin filaments, and were regulated by microtubules and substrate adhesion, and exhibited apparently independent fluctuation. The difference of strain energies associated with CC activities between leading versus trailing processes tightly correlated with the displacement of the soma at any given time. Application of brain-derived neurotrophic factor(BDNF) and Slit2, factors known to guide neuronal migration, at the leading process altered CC activities by regulating the small GTPases Cdc42 and Rho A, respectively, leading to forward and rearward soma translocation. These results delineate the multiple origins and spatiotemporal dynamics of the traction force underlying neuronal migration.

关键词： contraction center,neuronal migration,traction force,myosin-II,BDNF

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药物基因组学分析提示PTPRD基因多态性与非典型抗精神病药致体重增加关联

药物基因组学分析提示PTPRD基因多态性与非典型抗精神病药致体重...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者：郁昊王力芳吕路线马翠翠杜波卢天兰金超阎浩杨勇锋李文强阮燕燕张鸿燕张红星宓为峰马文斌栗克清张岱岳伟华北京大学精神卫生研究所/第六医院卫生部精神卫生学重点实验室暨国家精神心理疾病临床医学研究中心(北京大学) 北京大学-清华大学生命科学联合中心新乡医学院第二附属医院重点实验室河南省精神病医院锦州市康宁医院河北医科大学精神卫生研究所北京大学IDG麦戈文脑科学研究所

目的:抗精神病药治疗期间出现体重增加直接影响患者对治疗的依从性,已成为精神疾病治疗中的严重问题,应给予足够的重视。本研究采用药物基因组学研究方法,寻找与非典型抗精神病药引起的体重增加相关的单核苷酸多态性位点。方法:选择完成... 详细信息

目的:抗精神病药治疗期间出现体重增加直接影响患者对治疗的依从性,已成为精神疾病治疗中的严重问题,应给予足够的重视。本研究采用药物基因组学研究方法,寻找与非典型抗精神病药引起的体重增加相关的单核苷酸多态性位点。方法:选择完成8周非典型抗精神病药治疗的534例精神分裂症患者,进行全基因组单核苷酸多态性位点检测。随后选择同样治疗方案的精神分裂症568例患者作为独立验证样本,采用Sequenom平台进行测序。并针对只服用利培酮和喹硫平的236例患者进行单独分析。最后,针对显著关联的多态性位点进行表达数量性状分析(expression quantitative trait locus,e QTL)。结果:蛋白酪氨酸磷酸酶D型受体(protein tyrosine phosphatase,receptor type D,PTPRD)上的2个SNP位点,谷氨酰胺果糖-6-磷酸转氨酶2(glutamine:fructose-6-phosphate amidotransferase 2,GFPT2)上的1个SNP位点与非典型抗精神病致体重增加显著相关,多重检验矫正后3个SNP位点达全基因组显著关联水平(P<5×10-8)。该结果在独立样本中及只服用利培酮与喹硫平的患者中得到验证。eQ TL分析结果显示显著关联位点会影响所在基因的表达。结论:蛋白酪氨酸磷酸酶D型受体单核苷酸多态性与抗精神病药治疗导致汉族精神分裂症患者体重增加显著相关。

关键词：精神分裂症体重增加非典型抗精神病药药物基因组学单核苷酸多态性蛋白酪氨酸磷酸酶D型受体

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母孕期慢性温和性应激对子代成年大鼠类焦虑、抑郁行为以及GABA-A受体表达的影响

母孕期慢性温和性应激对子代成年大鼠类焦虑、抑郁行为以及GABA-A...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者：麻钰超李晓白中国医科大学附属第一医院心理科

目的:本研究通过观察母孕期慢性温和性应激以及类焦虑或抑郁行为对子代成年大鼠杏仁核、前额叶皮质GABA-A受体表达的影响,来探讨焦虑或抑郁症的发病机制,为临床治疗提供理论依据。方法:采用随机分组原则将孕鼠分为对照组和应激(PS)组。... 详细信息

目的:本研究通过观察母孕期慢性温和性应激以及类焦虑或抑郁行为对子代成年大鼠杏仁核、前额叶皮质GABA-A受体表达的影响,来探讨焦虑或抑郁症的发病机制,为临床治疗提供理论依据。方法:采用随机分组原则将孕鼠分为对照组和应激(PS)组。在孕期最后两周对应激组施加慢性温和性应激。月龄为3月大的子代进行高架十字迷宫和强迫游泳实验,观察其行为学的变化。运用蛋白印迹技术检测大鼠杏仁核、前额叶皮质GABA-A受体表达量的变化。结果:PS组子代雌、雄大鼠进入开放臂的相对次数和时间百分比明显减少,不动时间明显延长,表明PS组雌、雄子代类焦虑行为和类抑郁行为增多。蛋白印迹结果显示PS组雄性大鼠杏仁核GABA-A受体α1(P<0.001)和β1(P<0.01)亚基的表达低于控制组;PS组雌性大鼠杏仁核GABA-A受体α1亚基表达低于控制组(P<0.01),GAD67的表达高于控制组(P<0.05)。高架十字迷宫导致子代大鼠杏仁核α1亚基和β1亚基高于非高架十字迷宫组(行为主效应显著:P<0.001),雌性-高架-控制组α1亚基低于雌性-高架-PS组(PS与行为交互效应显著:P<0.05)。在前额叶皮质,高架十字迷宫组α1亚基高于非高架十字迷宫组(行为主效应显著:P<0.001);雄性-高架-控制组α1亚基高于雌性-高架-控制组(性别主效应显著:P<0.05)。强迫游泳导致子代杏仁核和前额叶皮质脑区α1亚基高于非强迫游泳组(行为主效应显著:P<0.001);杏仁核脑区强迫游泳组β1亚基高于非强迫游泳组(行为主要效应显著:P<0.001),雄性-强迫游泳-控制组α1亚基高于雌性-强迫游泳-控制组(性别主效应显著:P<0.05)。结论:1、母孕期慢性温和性应激使子代类焦虑、抑郁行为增多。2、母孕期慢性温和性应激显著减少了大鼠杏仁核中GABA-A受体的表达。3、母孕期慢性温和性应激和行为都会影响子代杏仁核与前额叶皮质GABA-A受体的表达并且GABA-A受体的变化与高焦虑、抑郁表现相一致,提示GABA-A受体可能参与了孕期应激所致的精神疾病的病理生理过程。

关键词：母孕期慢性温和性应激焦虑抑郁杏仁核前额叶皮质 GABA-A受体

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Study of effect and mechanism of electroacupuncture on the abnormal discharge of motor cortical neurons in 6-OHDA Rat

Study of effect and mechanism of electroacupuncture on the a...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Min Sun Jun Hua Liu Jun Jia Xiaomin Wang Key Laboratory of Neurodegenerative Disease of the Ministry of Education Capital Medical University

Althoughpharmacological dopamine replacement therapy and deep brain electrical stimulation(DBS) can alleviate the motor symptoms of Parkinson disease(PD), side effects of drugs and a small fraction of patients with PD can take advantage of DBS. A significantly less invasive method—electroacupuncture(EA)—has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through EA are unknown. In this study, unilateral injection of 6-hydroxydopamine(6-OHDA) was performed to set up a rat model of *** EA stimulation was used to analyze the effect on abnormal motor behaviors of PD rats. And at the same time, we detect the effect on motor cortex firing patterns after 4 weeks EA treatments to realize the intervention effect on motor cortex by EA stimulation. Here, we show EA gradually alleviates motor deficits in a rat model of PD. Neuronal recordings from motor cortex in parkinsonianrat revealed abnormalneural activityactivity in PD model. 100 Hz EA could downregulate beta oscillation, and also interfere with the Spike Triggered Average(STA) of beta oscillation, which was similar to the effect of L-dopa treatment, indicating that the motor cortex may be a potential taeget of EA stimulation.

关键词： Parkinson's disease,Electroacupuncture,Motor cortex,In vivo electrophysiology

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