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Membrane insertion of plasmalemmal precursor vesicles(PPV) is mediated by RablO interaction with MARCKS during axonal growth

Membrane insertion of plasmalemmal precursor vesicles(PPV) i...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Cai-Yun DENG~(**),Xiao-Hui XU~(**),Yang LIU,Tong WANG,Zhen-Ge LUO~* Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China

The formation of axons and dendrites and maintenance of the neuron's vastly expanded surface require the continuous addition of new *** axon extension,the coordination of membrane traffic,adhesion to extracellular substrate,and reorganization of the cytoskeleton at the peripheral region of the growth cone mediate the protrusive activity of the axon growth *** we have found the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles(PPV) during neuronal *** the mechanism of Rab10 action remains *** we report that the myristoylated alanine-rich C kinase substrate(MARCKS) interacts with Rab10 and mediates fusion of PPV to the plasma ***-regulation of MARCKs using siRNA against MARCKS abrogated polarized distribution of Rab10 and prevented neuronal ***, blockade of the interaction between Rab10 and MARCKS by over-expressing the MARCKS domain that mediated the RablO-MARCKS binding abolished membrane fusion of PPVs,which were labeled with BODIPY-ceramide. Membrane fusion of PPVs was also measured by analyzing the TIRF(Internal Reflection Fluorescence) signals of pHluorin-tagged receptors of axon growth promoting factors - TrkB for brain-derived neurotrophic factor(BDNF) and IGFR for insulin like factor 1(IGF-1).We found that down-regulation of MARCKS or blocking its interaction with Rab10 inhibited the TIRF ***,blocking the interaction between Rab10 and MARCKS inhibited axon growth in vitro and in ***,Rab10 interaction with MARCKS mediates fusion of PPV with the plasma membrane,a process required for axonal growth.

关键词： MARCKS Rab10 plasmalemmal precursor vesicle axonal growth fusion membrane insertion

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Wnt and cell polarity signaling in growth cone guidance

Wnt and cell polarity signaling in growth cone guidance

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yimin ZOU University of California,San Diego,USA

Although many extracellular axon guidance cues have been identified,the intracellular signal transduction and the cell biological mechanisms leading to directed navigation of the axon steering apparatus,the growth cone, remain vaguely *** family morphogens,presented in concentration gradients along the main body axes, are now well-accepted axon guidance cues,conserved from mammals to C *** signal through the Frizzled receptors to mediate axon attraction and *** of the Wnt-Frizzled signaling pathways is the highly conserved planar cell polarity(PCP) pathway,which establishes polarized cellular morphology along the plane of many different types of epithelial tissues in both vertebrates and *** found the core PCP components are required for Wnt5a-stimulated outgrowth and anterior-posterior guidance of commissural axons in the spinal ***1 can inhibit PCP signaling by increasing hyperphosphorylation of Frizzled3 and preventing its ***2 antagonizes that by reducing Frizzled3 phosphorylation and promotes *** commissural axon growth cones,Vangl2 is predominantly localized on the plasma membrane and is highly enriched on the tips of the filopodia as well as in patches of membrane where new filopodia *** together,we propose that the antagonistic functions of Vangl2 and Dvl1(over Frizzled3 hyperphosphorylation and endocytosis) allows sharpening of PCP signaling locally on the tips of the filopodia for sensing directional cues,Wnts,eventually causing turning of growth *** previous studies identified that atypical protein kinase C,a key component of the apical-basal polarity pathway which sets up cell polarity along the apical-basal axis,perpendicular to PCP,in many epithelial tissues,is also essential for mediating Wnt-Frizzled attraction and axon *** findings suggest that growth cone may be able to polarize themselves using cell polarity pathways and that the cell

关键词： Wnt and cell polarity signaling in growth cone guidance

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Targeting A-type K+ channels in primary sensory neurons for bone cancer pain in a rat model

Targeting A-type K+ channels in primary sensory neurons for ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Kai-Zheng DUAN~(1,*),Qian XU~(1,*),Xiao-Meng ZHANG~1,Zhi-Qi ZHAO~1,Yan-Ai MEI~2,Yu-Qiu ZHANG~(1,*) 1 Institute of Neurobiology,2 School of Life Sciences,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

The treatment of bone cancer pain remains a clinically challenging ***,we report that A-type K channels in primary sensory neurons are involved in the neuropathy of rat bone cancer pain and are a new target for diclofenac,a non-steroidal anti-inflammatory drug that can be used for therapy for this distinct *** injection of diclofenac dose-dependently attenuated bone cancer-induced spontaneous pain,mechanical allodynia and thermal hyperalgesia,all of which were reversed or prevented by administration of the A-type K channel blockers 4-AP or pandinotoxin-Kαor with siRNA targeted against Kv1.4 or ***,diclofenac significantly inhibited action potential firing and rapidly increased A-type K currents in IB4-positive small dorsal root ganglion （DRG） neurons in both normal and bone cancer ***,in bone cancer rats the A-type K currents were significantly increased on post-tumor day 14（PTD 14）;they then faded,but they still remained at a higher level on PTD ***,the expression levels of the A-type K channels Kvl.4,Kv3.4,and Kv4.3 showed timedependent changes during bone cancer *** diclofenac administration not only decreased soft tissue swelling adjacent to the tumor but also attenuated bone *** results indicate that A-type K channel modulators may provide a novel mechanism-based therapeutic strategy for bone cancer pain.

关键词： A-type K+ currents bone cancer pain diclofenac dorsal root ganglion rat

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Neuromedin U inhibits T-type Ca2+ channel currents and decreases membrane excitability in small dorsal root ganglia neurons in mice

Neuromedin U inhibits T-type Ca2+ channel currents and decre...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Fen WANG,Jin TAO~* Department of Neurobiology,Medical College of Soochow University,Suzhou 215123,China

Neuromedin U（NMU） has recently been reported to play a role in ***,to date,the relevant mechanisms still remain *** the present study,we investigated the expression profile of NMU receptors in mouse dorsal root ganglia（DRG） and identified a novel functional role of NMU in modulating T-type Ca channel currents（T-currents） as well as membrane excitability in small DRG *** found that NMU inhibited T-currents in a dose-dependent manner in mouse small DRG neurons that endogenously expressed NMU type 1 （NMUR1）,but not NMUR2 ***（1μM） reversibly inhibited T-currents by～27.4%.This inhibitory effect was blocked by GDP-β-S or pertussis toxin（PTX）,indicating the involvement of a Gα-*** depolarizing prepulse or intracellular application of QEHA,a synthetic peptide which competitively blocks G-proteinβγsubunit(G) mediated signaling,we found the absence of functional coupling between G and T-type Ca *** of the cells with H89,a protein kinase A（PKA） inhibitor,or intracellular application of PKI 5-24,blocked NMU-induced T-current inhibition,whereas inhibition of phospholipase C or protein kinase C elicited no such *** addition,we observed a significant decreased firing frequency of action potentials of small DRG neurons induced by NMU,which could be abrogated by pretreatment of the cells with NiCl（100μM）.Taken together,these results suggested that NMU inhibits T-currents via PTX-sensitive PKA pathway,which might contribute to its physiological functions including neuronal hypoexcitability in small DRG neurons in mice.

关键词： neuromedin U T-type Ca2+ channels dorsal root ganglia membrane excitability

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Inhibitor of MAPK/ERK kinase but not NMDA receptor antagonist blocks the survival-promoting effect of learning on immature neurons in hippocampus

Inhibitor of MAPK/ERK kinase but not NMDA receptor antagonis...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Zhi-Wei XU**,Yong-Hong WU**,Fei-Long Zhang,Yan GAO,Cheng-Gang ZHANG~* Beijing Institute of Radiation Medicine,State Key Laboratory of Proteomics,Beijing 100850,China

There is growing evidence demonstrating that hippocampus-dependent learning can rescue the newly generated neurons from apoptotic cell death,but the underlying mechanism is largely *** we explored the role of ERK signaling pathway in survival-promoting effect of hippocampus-dependent *** were injected intraperitoneally with bromodeoxyuridine(BrdU) to label dividing *** week later,the mice were trained in Morris water maze for five consecutive ***327(30 mg/kg),an inhibitor of the upstream MAPK/ERK kinase (MEK) and MK801(0.14 mg/kg),an antagonist of NMDA receptor were injected 30 min respectively before training. Level of extracellular signal-regulated kinase(ERK) phosphorylation was characterized using Western *** of BrdU-labeled cells in dentate gyrus was then *** showed that spatial learning enhanced the survival of immature neurons generated before ***327 did not produce significant impairment in escape latency of spatial learning,although SL327 down-regulated levels of hippocampal ERK ***,SL327 blocked the survival-promoting effect of *** contrast,MK801 increased the phosphorylation levels of ERK in hippocampus of the ***,MK801 also disrupted the performance of mice on spatial learning and decreased swimming speed of the ***,MK801 did not modulate survival-promoting effect of learning. Taken together,our results demonstrate that learning tasks enhance survival of new neurons through ERK-dependent signaling mechanisms but not mediated by activation of NMDA receptor in *** current study might provide a possible regulatory strategy of compensating neurogenesis losses associated with neurodegeneration disease and nonpathological ageing.

关键词： neurogenesis cell survival learning ERK NMDA receptor

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Modulation of theta and gamma oscillations in central olfactory pathway by behavioral state

Modulation of theta and gamma oscillations in central olfact...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Qing LIU~(1,3),Rui-Qi WU~(1,3),An-An LI~1,Fu-Qiang XU~(1,2,*) 1 Wuhan MRC,State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics,Wuhan Institute of Physics and Mathematics,the Chinese Academy of Science,Wuhan 430071,China 2 Wuhan National Laboratory for Optoelectronics,Wuhan 430074,China 3 Graduate University of Chinese Academy of Science,Beijing 100049,China

Objective In mammalian olfactory pathway,the oscillatory activities of the olfactory bulb(OB),piriform cortex(PCX)and hippocampus(HPC)have been extensively studied to elucidate odor information processing. However,less is known about the oscillations of spontaneous activity and the modulation by behavioral state, especially for the theta(4-12 Hz)and gamma(35-100 Hz)*** In the present study,local field potentials (LFP)of spontaneous activity were recorded from the OB,PCX and HPC simultaneously in awake and anesthetized *** Compared with the anesthetized state,awake mice showed increased theta and gamma oscillations in all the three regions,but decreased coherences among ***,the spontaneous activities in exploratory walking and motionless mice were *** exploratory state,the power of theta oscillations in the PCX and HPC was decreased,whereas the power of theta in the OB and gamma in all regions were increased significantly. However,the coherences among the three brain regions for both theta and gamma oscillations were significantly *** was also found that the coherence between the PCX and the HPC was always the highest regardless of brain *** These results suggest that the theta and gamma oscillations in central olfactory pathway could be modulated by behavioral state,and that the higher coherences of both theta and gamma oscillations between PCX and HPC indicate tighter functional coupling between them.

关键词： oscillation olfactory bulb piriform cortex hippocampus functional coupling

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Neural coding of nociceptive stimulus intensity in the rat medial and lateral pain pathways

Neural coding of nociceptive stimulus intensity in the rat m...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Ning WANG~1,Yang ZHANG~2,Jin-Yan WANG~1,Fei LUO~(1,*) 1 Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Sciences,Beijing 100101,China 2 Neuroscience Research Institute and Department of Neurobiology,Peking University Health Science,Beijing,China

Objective The ability to encode the intensity of a painful stimulus is an essential component of the neural processes involved in pain *** is well accepted that stimulus intensity is encoded by sensory pathways. However,the role of the affective pathway in the processing of noxious stimulus intensity is *** this study, we hypothesized that neurons in the medial pathway may also play a role in noxious stimulus intensity coding, and that spike counts may best convey information related to stimulus *** Multichannel singleunit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following application of painful laser stimuli to the *** brain regions were monitored,including two that are associated with the lateral sensory pain pathway,namely the ventral posterior lateral thalamic nucleus(VPL)and the primary somatosensory cortex(SI),and two that are associated with the medial pathway involved in affective aspects of pain perception,namely the medial dorsal(MD)thalamic nuclei and the anterior cingulate cortex(ACC).Neuron number coding,firing rate coding,and spike count coding were examined in this *** Our results show that neurons in the affective pathway can encode noxious stimulus intensity,and this capability appears to be comparable to that in the sensory *** also found that optimal intensity discrimination depends on the collective contributions of both pain *** This study draws attention to the role of the affective pain pathway in the processing of noxious ***,we provide evidence that spike count coding may be the most reliable method for examining sensory processing in the brain.

关键词： laser stimulation intensity pain single unit spike count

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Involvment of BNIP3 in the antidepressant's effects on the hippocampal neuroplasticity

Involvment of BNIP3 in the antidepressant's effects on the h...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xin-Hua HE,Shu-Ji LI,Xin-Hong ZHU,Tian-Ming GAO~* Department of Neurobiology,College of Basic Medical Sciences,Southern Medical University,Guangzhou 510515, China

Objective Depression is a common mental disorder with high prevalence,high disability rate and high suicide rate,and severely impairs human lives and *** studies have shown that depression has a close relationship with abnormal hippocampal *** this process is thought to be a new strategy for rapid *** the key moleculars that regulate this kind of hippocampal neuroplasticity is expected to find candidate targets for ***,little is known about the molecular mechanism for antidepressants regulating *** present research aimed at exploring whether Bcl-2/adenovirus E1B 19 kD-interacting protein 3(BNIP3) participates in antidepression by regulating the hippocampal neuroplasticity,providing experimental evidences for finding candidate and rapid antidepressant targets for depression *** The expression of BNIP3 is quantified by real-time PCR and western blot during the key period of the development of the dendrite, spine and synapse formation of hippocampal *** of BNIP3 and RNA interference methods were used to determine the influence of BNIP3 on dendrite arbors of hippocampal *** real-time PCR and western blot methods to quantify the exprEssion of BNIP3,synapsinl and GluRI after the administration of imipramine and ***(1) BNIP3 continued to increase during the critical period of the dendrite,spine and synapse formation of hippocampal neuron in culture.(2) Antidepressants imipramine and fluoxetine could increase the expression of BNIP3,synapsinl and GluRI in hippocampal neuron.(3) Overexpression of BNIP3 increased the number of dendrite arbors of hippocampal neuron,while BNIP3 siRNA has no influence on the number of dendrite arbors of hippocampal *** BNIP3 may participate in the antidepressant's effects on the hippocampal neuroplasticity.

关键词： BNIP3 depression neuroplasticity hippocampus

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Action potential dependent inward current on the oligodendrocyte in mouse cortex

Action potential dependent inward current on the oligodendro...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Hao QIAN,Jin-Hui WANG~* State Key Laboratory of Brain and Cognitive Sciences,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

Objective Oligodendrocyte that forms the myelin in central nervous system has been described as the passive support cell to insulate the axon for *** individual oligodendrocyte supports 1-50 myelin sheaths and accelerates the action potential propagation by reducing the ion leakage and capacitance of cell ***, recent studies indicate that oligodendrocyte depolarizes during the population activity of surrounding neurons,which suggests some potential active functions of *** the mechanism of this reaction is still ***, we use whole cell patch recording to monitor the oligodendrocytic response to neuronal activity,which would be helpful to identify the relationship between them and clarify the oligodendrocytic effects on the propagation of action *** In order to identify oligodendrocyte in brain slice,a transgenic mouse that expresses enhanced green fluorescence protein(EGFP)driven by the 2',3'-cyclic nucleotide 3'-phosphodiesterase(CNP)promoter (CNP-EGFP)was used in our *** performed paired whole cell recordings from a pyramidal neuron and an oligodendrocyte of layer 5 in cerebral *** paired cells were filled with two different cell-impermeable fluorescent dyes through recording pipettes,which was used to trace these cells and identify the relationship between their ***(1)An inward current was recorded on an oligodendrocyte when a spike was propagating on the axon wrapped by this *** the oligodendrocyte didn't connect with the paired pyramidal cell,no response was observed.(2)This current consists of two phases:a fast one and a slow *** amplitude of the fast phase increased when the oligodendrocyte was depolarizing,while that of the slow phase decreased.(3)The blockers of voltage-gated calcium channel,ionic glutamate receptors,glutamate transporters and gap junction all had no effect on the amplitudes of these two *** totally blocked the slow phase bu

关键词： oligodendrocyte axon myelin action potential propagation clearance of potassium

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A Cl--regulated structural switch that controls proton sensitivity of acid-sensing ion channels

A Cl--regulated structural switch that controls proton sensi...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei-Guang LI~(1,2),Zhu-Dan ZHANG~(1,2),Hui CAO~1,Tian-Le XU~(1,3,*) 1 Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031 2 Graduate School of Chinese Academy of Sciences,Shanghai 200031,China 3 Institute of Medical Sciences,Shanghai Jiaotong University,Shanghai 200025

Acid-sensing ion channel（ASIC） has a prominent role in tissue pH-sensing and neuronal signaling,and participates in various pathological *** the availability of structures for chicken ASIC1 subunit, obtaining mechanistic insight into the function of these highly dynamic channel proteins using static crystallographic information is *** a series of mutational,chemical and functional approaches,we found that the extracellular CI-binding module shown in crystals of ASIC1 constitutes an indispensable component for ASIC1a *** gluconate-substitution of natural CI-binding enhanced whereas engineering a permanent anion into the CI-binding module inhibited channel activity,suggesting an essential role of CI-regulated domain flexibility but not the absolute charge state created by bound anion in channel ***-comparable anion substitution（F, Br-,or I） revealed a CI-dependent modulation of proton sensing function,supporting a structural role of dynamic association and dissociation of CI ion in coordinating conformational transition associated with proton sensing. Furthermore,charge reversal and swap as well as mutant cycle analysis of alanine substitutions of two counter-charged residues（K311,E315） in the CI-binding module show that they electrostatically interacted and energetically coupled, underpinning a structural switch controlling proton sensitivity of ASIC1a channels.

关键词： acid-sensing ion channel channel gating salt bridge

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