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Rapid effect of estrogen on glutamate related synaptic transmission and plasticity in the anterior cingulate cortex

Rapid effect of estrogen on glutamate related synaptic trans...

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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： Xiao XIAO,Yan ZHANG,Zhi-Qi ZHAO,Yu-Qiu ZHANG~* Institute of Neurobiology,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

Classically,estrogen has multiple actions in the brain via genomic mechanisms which generally take several *** present study was designed to examine that whether estrogen regulates glutamatergic transmission and plasticity within minutes and what is the possible mechanisms underlying the estrogen-induced rapid effects in the anterior cingulate cortex(ACC).Immunohistochemistry results revealed that estrogen receptors(ERs) were highly expressed in glutamatergic neurons of the ***-cell recording from ACC slices results showed that estrogen enhanced the glutamatergic excitatory postsynaptic currents(EPSCs) in a dose-dependent ***,the affect of estrogen on AMPA and NMDA transmission exhibited an opposite manifestation:NMDA-mediated EPSCs(NMDAEPSCs) were significantly enhanced;whereas AMPA-EPSCs were remarkably *** fast onset effect of enhanced NMDA-EPSCs,within 6 minutes bath application of estrogen,lasted for more than 30 minutes(NMDA- LTP).This NMDA-LTP was blocked by ER antagonist(ICI 182780) and was mimicked by E-BSA,a specific agonist of membrane ***,the induction of estrogen-induced NMDA-LTP was also prevented by NR2B inhibitor and PKA *** together,these findings implicate that estrogen has rapid effects on glutamate transmission in ACC ***,estrogen-induced chemical NMDA-LTP is at least partially mediated by membrane ***2BPKA pathway may play a critical role in estrogen-induced NMDA-LTP.

关键词： estrogen rapid effect NMDA receptor LTP anterior cingulate cortex

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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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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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Immunoexpression of synaptophysin(SYN) and GABA in the outer part of rat retina following acute high intraocular pressure

Immunoexpression of synaptophysin(SYN) and GABA in the outer...

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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： Jia LUO,Hui WANG,Dan CHEN~*,Ju-Fang HUANG Department of Anatomy and Neurobiology,Xiangya School of Medicine,Central South University,Changsha 410013, China

Objective To investigate the changes of synaptic plasticity in the outer part of rat retina and whether GABAergic neurons being involved in following acute high intraocular pressure（HIOP）.Methods The intraocular pressure of all left eyes was increased until b wave of flash electroretinogragh（fERG）disappeared and such pressure maintained for 60 *** right eyes served as normal *** SD rats were sacrificed respectively on hour 2, 6,12 or day 1,3,7,14 following *** staining and western blot were used to detect the expression of SYN and GAB *** In the outer part of retina,SYN was mainly located in the outer plexiform layer（OPL）in normal *** HIOP 2 h,6 h,12 h,1 d,3 d and 7 d,SYN positive products were extended to the inner part of the outer nuclear layer（ONL）.The expression of SYN in the outer part of retina was similar to the normal condition 14 d after *** was mainly located in the inner nuclear layer（INL）and the inner part of OPL in normal *** HIOP 2 h,6 h,12 h,1 d,3 d and 7 d,GABA expression in OPL was downregulated, while upregulated in *** the 7day,there was silkiness positive product in ONL,which was not double-staining with *** the 14day after HIOP,the positive product was *** There is synaptic plasticity in rat OPL and ONL following HIOP insult,GABA positive neuron may not participate directly in this process.

关键词： HIOP retina synaptophysin GABA

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Activation of translocator protein(TSPO) reverses neuropathic pain behavior

Activation of translocator protein(TSPO) reverses neuropathi...

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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： Xu-Hong WEI,Li-Jun ZHOU,Cui-Cui LIU,Xiao WEI,Xian-Guo LIU~* Pain Research Center of Sun Yat-sen University,Guangzhou 510080,China

Neuropathic pain is characterized by a heightened painful response to noxious(hyperalgesia) or innocuous(allodynia) stimulation,and pain at rest(spontaneous pain).At present no effective drug is available for the clinical symptom.A recent study has shown that the translocator protein(TSPO,18 kDa),a peripheral receptor for benzodiazepine,modulates pain behaviors of rats induced by *** the present study,we evaluated the role of TSPO in neuropthic pain produced by L5 spinal nerve ligation(L5 SNL) with use of behavioral testing, immunohistochemistry and Western blot *** found that TSPO was up-regulated in spinal dorsal horn following L5 SNL and the change lasted until behavioral signs of neuropathic pain diminished(around 50 d).Double immunofluorescence showed that in naive rats,TSPO was located mainly in astrocytes,to a lesser extent in neurons, but not in microglia,whereas following L5 SNL,TSPO was upregulated in astrocytes and microglia,but not in *** data showed that single intrathecal injection of TSPO agonist Ro5-4864 or FGIN-1-27 reversed established mechanical allodynia induced by L5 SNL *** and Western blot showed that intrathecal injection of Ro5-4864 reversed activation of astrocytes,and depressed p38 MAPK activation,which is exclusively activated in spinal microglial cells following peripheral nerve *** data suggested that activation of TSPO by agonists might reverse neuropathic pain by inhibition of activated glial cells.

关键词： TSPO neuropathic pain astrocyte

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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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Restoration of visual function by ectopic expression of melanopsin in rd mice

Restoration of visual function by ectopic expression of mela...

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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： Amane Koizumi Nobushige Tanaka Satchidananda Panda Richard H.Masland Harvard Medical School BostonMA 02114USA The Salk Institute for Biological Studies La JollaCA 92037

The principal photoreceptors for image forming vision in the retina are rod and cone *** of photoreceptor cells,as happens in a number of human diseases,such as retinitis pigmentosa and age-related macular degeneration,leads to irreversible ***,the current therapeutic treatment for retinal degeneration is very ***,we asked whether *** possible to restore any vision by ectopic expression of melanopsin,a newly discovered light-sensitive photopigment,in the surviving ganglion *** protein melanopin is normally expressed in 2%-3%of ganglion cell population of the mouse *** test this intriguing possibility,we used a viral vector to express mammalian melanopsin in other retinal ganglion cells of rd/rd mice,which suffer an early degeneration of rod photoreceptors and a subsequent degeneration of *** each retina melanopsin was expressed in up to 6000 retinal ganglion cells,of many morphological ***-cell patch-clamp recording showed intrinsic photoresponses in these cells,even after degeneration of the photoreceptors and additional pharmacological or Cd block of synaptic *** newly melanopsin-expressing ganglion cells provided an enhancement of visual function in the rd/rd mice:the pupillary light reflex returned almost to normal;the mice showed behavioral avoidance of light in an open field test;and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. These results show that an effective signalling pathway for melanopsin is not restricted to the retinal ganglion cells that normally contain melanopsin,or to any particular ganglion cell *** of this or other light-sensitive proteins in the surviving retinal neurons might provide some degree of vision for humans blind due to photoreceptor degeneration.

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Contribution of GABAA receptor-mediated activity to self-generated oscillations in hippocampal CA3-CA1 regions

Contribution of GABAA receptor-mediated activity to self-gen...

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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： Yan YANG,Xiao-Lin XUE,Chao DING,Zhi-Ru WANG~* Plasticity of Neural Circuit Lab,Key Laboratory of Brain Functional Genomics,Ministry of Education,East China Normal University,Shanghai 200062,China

Objective Spontaneous oscillations in the hippocampus are believed to play important roles in hippocampus-dependent cognition and learning and *** studies in hippocampal slices indicate that these oscillations are mediated by the activity of intemeurons in the hippocampus,particularly via GABAA receptors. This issue remains to be further *** In this study,we developed a new system of in vitro wholecell patch-clamp recordings in whole-hippocampus *** In such preparation,robust spontaneous oscillations（from 0.8 Hz to 2 Hz）were observed in both pyramidal cells and intemeurons in the absent of any *** whole-cell recordings further revealed that the oscillations were synchronized in CA1, CA3,and across CA1-CA3 *** the presence of bicuculline-a GABA receptor blocker-in bath solution,the frequency of spontaneous oscillations was remarkably reduced to 0.1-0.2 Hz,which was found in the pyramidal cells and intemeurons of both CA1 and CA3 ***,extracellular blockade of GABA receptors by SCH50911 didn't alter the frequency of the *** treatment of ZD7288,which blocks hyperpolarization-activated （I）channels,also slowed down the hippocampal oscillations to .4 *** Our observations from whole-hippocampus formation revealed the important roles of GABA receptors,probably coordinating with the activity of I channels,in mediating the self-generated oscillations in the hippocampus in the absence of extrahippocampus inputs.

关键词： hippocampus oscillation GABAA receptor Ih channel

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Derepression of tPA expression by knocking out NRSF enhances mature BDNF and upregulates hippocampal LTP

Derepression of tPA expression by knocking out NRSF enhances...

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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： Xue-Wen CHENG,Lei CAI,Bin LU,Da-Feng XU,Li HUANG,Li XU,Jing ZHENG,Jian FEI,Zhi-Qi XIONG~(1*) 1 Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,320 Yueyang Road,Shanghai 200031,China 2School of Life Sciences and Technology,Tongji University,1239 Siping Road,Shanghai 200092,China 3School of Pharmacy,East China University of Science and Technology,130 Meilong Road,Shanghai 200237,China

Neuronal restrictive silencing factor(NRSF)is an epigenetic repressor with important role in regulating neurogenesis and ***,the physiological function of NRSF in postnatal brain remains an interesting ***,we reported that activity-dependent synaptic plasticity was suppressed by *** cre/ loxP system,nrsf was conditionally knockout(cko)in forebrain excitatory *** recording of hippocampus CA1 radiatum area revealed a significantly upregulated long-term potentiation(LTP).We also found that activity stimulation led to significant enhancement of mature BDNF in cko mice,and this enhancement was mediated by the increased level of tissue plasminogen activator(tPA).Moreover,we found tPA was transcriptionally repressed by NRSF through direct binding to RE1 sequence in tPA *** of tPA activity abolished the upregulation of LTP in nrsf-cko *** findings provide an NRSF mediated epigenetic mechanism that moderates LTP in the hippocampus CA3-CA1 pathway.

关键词： NRSF LTP tPA synaptic plasticity

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Drosophila FMRP regulates microtubule network formation and axonal transport of mitochondria

Drosophila FMRP regulates microtubule network formation and ...

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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： Aiyu YAO~1,Shan JIN~(1,2),Xin-Hai LI~1,Zhi-Hua LIU~1,Xue-Hua MA~1,Jing TANG~1,Yong Q.ZHANG~(1,*) 1 Key Laboratory of Molecular and Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China 2 College of Life Sciences,Hubei University,Wuhan 430062,China

Fragile X syndrome,the most common form of inherited mental retardation,is caused by the absence of the fragile X mental retardation protein *** RNA-binding FMRP represses translation of the microtubule-associated protein IB(MAPIB) during synaptogenesis in the brain of the neonatal ***,the effect of FMRP on microtubules remains *** evidence shows that the structure and function of FMRP are well conserved across species from Drosophila to *** a genetic screen,we identified spastin as a dominant suppressor of rough eye caused by dfmrl over-expression,spastin encodes a microtubule-severing protein and its mutations cause neurodegenerative hereditary spastic *** and biochemical analysis revealed that dfmrl acts at upstream of or in parallel with spastin in multiple processes,including synapse development,locomotive behaviour and microtubule network *** showed that both loss- and gain-of-function mutations of dfmrl result in an apparently altered microtubule *** analysis revealed that the levels of a-tubulin and acetylated microtubules remained normal in dfmrl mutants but increased significantly when dfmrl was over-expressed. To examine the consequence of the aberrant microtubules in dfmrl mutants,we analyzed the microtubule-dependent mitochondrial transport and found that the number of mitochondria and the flux of mitochondrial transport were negatively regulated by *** results demonstrate that dFMRP has a crucial role in controlling microtubule formation and mitochondrial ***,defective microtubules and abnormal mitochondrial transport might account for,at least partially,the pathogenesis of fragile X mental retardation.

关键词： Drosophila FMRP regulates microtubule network formation and axonal transport of mitochondria

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