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Mifepristone repairs alteration of learning and memory abilities in rat model of depression

Mifepristone repairs alteration of learning and memory abili...

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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： Jian-Dong SUN,Yan LIU,Yu-He YUAN,Nai-Hong CHEN~* Key Laboratory of Bioactive Substances and Resources Utilization,Ministry of Education,Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

Objective To study the amelioration effect of glucocorticoid receptor(GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression and explore mechanisms *** In the present study,we used a 35-d rat chronic unpredictable stress(CUS) model to observe both depression-like behaviors in sucrose preference test(SPT) and open-field test(OFT) and learning and memory-associated behaviors in Morris water maze test.A total of 36 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size:control group(CON);CUS group(CUS);CUS + mifepristone group(CM).Animals in CM group were first exposed to CUS for 14 d,and then were administered with 50 mg/kg per day of mifepristone with continued CUS *** EIA Kit was used to detect the concentration of plasma corticosterone(CORT).Nissl staining was used to observe the structure of *** The results demonstrate that CUS exposure induces both depressive-like and learning and memory-associated behaviors and that these deficits are reversed by *** to CON group,the concentration of plasma CORT increased significantly in CUS group. We also found that CUS exposure damaged the structure of hippocampus,whereas mifepristone had an amelioration *** The results indicate that the structural deficits of hippocampus resulting from long-term stress exposure,which could contribute to the impairment of learning and memory in depression,are reversed by the GR receptor antagonist mifepristone.

关键词： mifepristone chronic unpredictable stress learning and memory depression corticosterone hippocampus

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Potassium channel of oligodendrocyte precursor cells during perinatal hypoxia-ischemia

Potassium channel of oligodendrocyte precursor cells during ...

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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： Peng-Hui CHEN,Wen-Qin CAI~* Department of Neurobiology,Chongqing Key Laboratory of Neurobiology,Third Military Medical University, Chongqing 400038,China

Objective Oligodendrocyte precursor cells(OPC)are particularly susceptible to perinatal hypoxia-ischemia resulting in decreased myelination and infant cerebral *** precise mechanism remains *** recordings from these cells have revealed that they possess unique potassium channel properties,which are distinct from the traditional class of glial cell and *** study is to explore whether rectified potassium channel of OPC is involved in hypoxia ischemic brain *** Whole cell voltage dependent ion channels were recorded by patch clamp technology in acute brain slices of postnatal 7 days rats after hypoxia-ischemia 2 *** recorded cell,which was injected intracellular Lucifer yellow,was identified with the marker NG2 by fluorescent ***(1)Sodium to potassium conductance ratio was decreased,owing to the increase of inward sodium current amplitude.(2)Outward rectified potassium channel exhibited rectify fall off.(3)There was no significant difference in variable rectified potassium channel and inward rectified potassium channel.(4)Tail current and activation voltage were all raised,which reduced activation and inactivation of potassium *** Outward rectified potassium channel and tail current of potassium channel play more important role in OPC susceptible to hypoxia ischemia.

关键词： oligodendrocyte precursor cell(OPC) patch clamp hypoxia-ischemia potassium channel rectify

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Functional connectivity among cortical regions is shaped by associative experiences

Functional connectivity among cortical regions is shaped by ...

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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 LIU National Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University

＜正＞The emergence of coherent cognition and behavior relies on the coordination of scattered mosaics of functionally-specialized brain ***,little is known about how the neural mechanisms that coordinate this distributed brain activity are *** proposed that brain regions are organized dynamically into functional groups by the temporal structure of their neural activity as co-activation of brain regions leads to the Hebbian strengthening of the functional connectivity between *** test this hypothesis,we trained subjects to learn the association between photos of houses and Chinese characters,and then examined whether the coherence between BOLD signal fluctuation in the parahippocampal place area（PPA） and that in the visual word form area（VWFA） increased after the *** found that the training not only improved the behavioral performance in pairmatching task but more increased the functional connectivity between the PPA and *** increased coherence was not due to the mental imagery of the associated stimulus（***） when a trained stimulus（***） was presented,because the activation level of the trained houses in the VWFA was unchanged between before and after ***,these findings suggest that the functional connectivity between co-activated regions,not their individual activation,may be the material basis of mental ***,when the PPA was activated by untrained house or scene stimuli,the neural activity in the VWFA fluctuated in a coherent fashion,suggesting that the propagation of the temporal structure in neural activation from one node to another is not stimulus *** the other hand,the increased coherence was limited to coactivated regions as the connectivity strength between the VWFA and the lateral occipital complex（LOC） and that between the PPA and the LOC were *** sum,our results provided an example of how large-scale integration is formed through Hebbian learning.

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Ghrelin inhibits visceral afferent activation of catecholamine neurons in the solitary tract nucleus

Ghrelin inhibits visceral afferent activation of catecholami...

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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： SM Appleyard Program in Neuroscience Department of Veterinary Comparative AnatomyWashington State University School of Life Science Northeast Normal University

＜正＞Brainstem A2/C2 catecholamine（CA） neurons in the solitary tract nucleus（NTS） are thought to play an important role in the control of food intake and other homeostatic *** have previously demonstrated that these neurons,which send extensive projections to brain regions involved in the regulation of appetite,are strongly and directly activated by solitary tract（ST） visceral ***,a potent orexigenic peptide released from the stomach,is proposed to act in part through modulating NTS CA neurons but the underlying cellular mechanisms are ***,we identified CA neurons using transgenic mice that express enhanced green fluorescent protein driven by the tyrosine hydroxylase promoter（TH-EGFP）.We then determined how ghrelin modulates TH-EGFP neurons using patch-clamp techniques in a horizontal brain slice *** inhibited the frequency of spontaneous glutamate inputs（spontaneous EPSCs） onto TH-EGFP neurons,including cholecystokinin-sensitive neurons,an effect blocked by the GHSR1 antagonist,*** resulted in a decrease in the basal firing rate of NTS TH-EGFP neurons,an effect blocked by the glutamate antagonist *** also dose-dependently inhibited the amplitude of ST afferent-evoked EPSCs（ST-EPSCs） in TH-EGFP NTS neurons,decreasing the success rate for ST-evoked action *** addition,ghrelin decreased the frequency of mini-EPSCs suggesting its actions are presynaptic to reduce glutamate ***,inhibition by ghrelin of the ST-EPSCs was significantly increased by an 18 h *** results demonstrate a potential mechanism by which ghrelin inhibits NTS TH neurons through a pathway whose responsiveness is increased during fasting.

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Activation of 5-HT3 receptor disrupts development of gamma oscillations in hippocampal CA1

Activation of 5-HT3 receptor disrupts development of gamma o...

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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： Kristopher YOON Ho KO Alexei MOROZOV Unit on Behavioral Genetics Laboratory of Molecular PathophysiologyNIMHNIHUSA Department of Neuroscience Physiology & PharmacologyUniversity College LondonUK

5-HT3 receptor has been implicated in learning and memory *** of this receptor has been suggested to impair cognition whereas its inhibition is thought to facilitate *** oscillations are proposed to play an important role in cognition and memory;however,the role of 5-HT3 receptor in gamma oscillations remains *** gamma oscillations are driven by interplay between fast-spiking parvalbumin(PV)- positive interneurons and pyramidal cells,the roles of other interneurons are poorly understood.A subpopulation of PV-negative but cholecystokinin(CCK)-positive hippocampal interneurons expresses 5-HT3 *** we investigated how 5-HT3 receptors modulate carbachol-induced gamma oscillations through these interneurons in hippocampal area CA1.5-HT3 receptor agonist m-CPBG attenuated development of gamma *** increased afterhyperpolarization(AHP)and reduced firing frequency in 5-HT3 cells in a Ca-and small conductance potassium (SK)-channel-dependent manner,reduced inhibitory input to PV cells and increased but desynchronized PV cells’ firing,which interfered with the development of gamma *** findings provide a novel mechanism whereby 5-HT3 interneurons modulate gamma oscillations by changing inhibition of PV interneurons,which might be involved in the modulation of cognitive functions by 5-HT3 receptors.

关键词： 5-HT3 receptor gamma oscillation hippocampus PV interneurons CCK cells firing frequency accommodation

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Kinetics of vesicle reuse at the Calyx of Held synapses

Kinetics of vesicle reuse at the Calyx of Held synapses

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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-Feng QIU,Qian-Wen ZHU,Jian-Yuan SUN~* Institute of Biophysics,Chinese Academy of Sciences,State Key Laboratory of Brain and Cognitive Science,Beijing 100101,China

Vesicle recycling and reuse is essential in maintaining synaptic *** spite of accumulative studies,it remains elucidated that how many vesicles involve in recycling,how long and how fast a vesicle can be reused after *** made the whole cell recording of the excitatory postsynaptic currents（EPSCs）at a central synapse,the Calyx of Held,under the long duration of stimulation in the presence of folimycin,a vesicular ATPase inhibitor to annihilates the H gradient and block glutamate refilling of synaptic *** was confirmed that vesicles at the Calyceal synpases do recycle and reuse after *** long trains of 20 Hz or 50 Hz stimulation,the evoked EPSCs can be rapidly depressed and finally mostly vanished,implying the depletion of the recycling *** size of the recycling pool was thus estimated as 180,000-350,000 *** did not observe the rapid vesicle reuse within 10 s,which supports the notion that rapid endocytosis does not immediately recycle vesicles within the readily releasable *** comparison between stimulation evoked EPSCs with and without folimycin,we further described the kinetics of synaptic vesicle reuse with double exponential *** from the previous ways to predict and estimate the kinetics of vesicle recycling by endocytotic kinetics,this study proposed a quantitatively description of the kinetics of synaptic vesicle reuse at a central synapse based on direct *** further proposed two pathways of synaptic vesicle recycling with distinguished kinetics.

关键词： vesicle recycling reserve pool,readily releasable pool

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Stimulus specific adaptation in the cultured cortical network

Stimulus specific adaptation in the cultured cortical networ...

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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： Hai-Tao WANG,Yi-Fan HAN,Ju-Fang HE~* Applied Neuroscience Laboratory,Department of Rehabilitation Sciences,the Hong Kong Polytechnic University, Hong Kong,China

Stimulus specific adaptation(SSA)is widely demonstrated in many brain regions of human and intact animals from multiple spatial scales including extracellular units recording and *** models are proposed to explain that repetitive stimulus induces adaption of physiological responses to favor deviance stimulus detection in the network *** the present study,we would examine the SSA at the synapse level with whole cell patch clamp recording from the cultured cortical *** cultured pyramidal neurons shared the similar SSA properties in response to the odd-ball stimulation paradigm as those reported with in vivo *** different stimuli were from electrical stimulations that were spatially *** cultural neurons showed SSA to the electrical *** SSA was not attributable to a reduction of the intrinsic membrane properties in that cultured neurons faithfully followed the intracellular current injection up to 200 *** AMPA receptors mediated excitatory postsynaptic currents(EPSC)also displayed stronger SSA compared with the GABA receptors mediated inhibitory postsynaptic currents(IPSC).The different dynamic of short term synaptic depression characterized by EPSC and IPSC might account for the generation of SSA at the supra-threshold spike *** findings support that the synapse specific fatigue would be the candidate neural mechanism for the stimulus specific adaptation.

关键词： stimulus specific adaptation short term plasticity synaptically driven spikes EPSC IPSC

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Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain

Identification of an adenylyl cyclase inhibitor for treating...

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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： Susan S.KIM Kohei KOGA Giannina DESCALZI Kunjumon I.VADAKKAN Bong-Kiun KAANG Deparment of Physiology University of TorontoToronto M5S1A8Canada Institute of Neuroscience the Fourth Military medical UniversityXi'an 710032China

＜正＞Objective Neuropathic pain,often caused by nerve injury,is commonly observed among patients with different *** its basic mechanisms are poorly understood,effective medications are limited. Previous investigations of basic pain mechanisms and drug discovery efforts have focused mainly on early sensory neurons such as dorsal root ganglion and spinal dorsal horn neurons,and few synaptic-level studies or new drugs are designed to target the injury-related cortical plasticity that accompanies neuropathic *** previous work has demonstrated that calcium-stimulated adenylyl cyclase 1（AC1） is critical for nerve injury-induced synaptic changes in the anterior cingulate *** Rational drug design and chemical screening,a variety of behavioral tests, electrophysiological methods and toxicity studies were performed in the present *** It was identified that a lead candidate AC1 inhibitor,NB001,was relatively selective for AC1 over other adenylate cyclase ***001 has an analgesic effect in animal models of neuropathic pain,without any apparent side effects when administered intraperitoneally or *** AC1 could be a productive therapeutic target for neuropathic pain and describes a new agent for the possible treatment of neuropathic pain.

关键词： adenylyl cyclase anterior cingulate cortex neuropathic pain

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Glutamate activated spinal astrocytes are involved in the thermal hyperalgesia

Glutamate activated spinal astrocytes are involved in the th...

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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： Rui-Hong SHI,Xin ZHAO,Ce ZHANG~* Department of Physiology National Key Disciplines,Key Laboratory for Cellular Physiology of Ministry of Education,Shanxi Medical University,Taiyuan 030001,China

Objective Numerous evidence suggests that spinal astrocytes play an important role in chronic pain through release of neuroactive substances,such as interleukin and *** produces marked effects in initiation and transmission of nociceptive ***,there is a lack of direct evidence that how glutamate activate astrocytes and what's effects of activated astrocytes by glutamate on pain *** study therefore explored the direct effects of glutamate activation of spinal *** Primary culture of spinal astrocytes were administered with *** levels of protein and mRNA expression of IL-6,which reflect astrocyte activation, were determined by ELISA assay and real-time *** spinal astrocytes activated by glutamate were injected into the lumber enlargement of adult Wistar rats,and paw withdrawal latency(PWL) was *** Administration of glutamate(1 000 uM) activated astrocytes from 6 h after intrathecal injection and reached the maximal level at 24 h(the last time point we explored).Besides,glutamate(1 000 uM) enhanced the release of IL-6 by astrocytes. Intrathecal injection of cultured spinal astrocytes,which were stimulated by glutamate,induced a substantial decrease of PWL,indicating the development of thermal *** Our results suggest that activated astrocytes by glutamate is sufficient to produce thermal hyperalgesia in rats by releasing IL-6.

关键词： glutamate spinal astrocyte thermal hyperalgesia IL-6

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The role of proheparanase in synaptic plasticity of the hippocampus

The role of proheparanase in synaptic plasticity of the hipp...

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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： W.C.CHAM D.K.Y.SHUM Departments of Biochemistry and Physiology LKS Faculty of Medicinethe University of Hong Kong

Perineuronal heparan sulfate(HS)moieties are implicated in the modulation of neurotransmission by controlling the functional properties of AMPA-type glutamate *** hypothesize that neuronal mechanisms modulate peri-synaptic HS level,thereby regulating synaptic strength and *** address this,basal synaptic strength and long-term changes in synaptic efficacy in the Schaffer collateral pathway of the rat hippocampus were assessed in relation to strategies that perturb peri-synaptic *** hippocampal slices,heparitinase treatment led to dose-dependent attenuation of long-term potentiation(LTP)in correlation with loss of perineuronal HS *** heparanase expression was found at the CA1 hippocampal neurons,we further tested if heparanase is the mammalian counterpart of heparitinase in the regulation of synaptic strength/*** asked therefore if neuronal heparanase is secreted as the pro-form or the active *** phorbol ester stimulation of hippocampal neurons in culture, pericellular proheparanase accompanied by increase in enzymatically active heparanase in the cytoplasmic fraction was revealed by Western blot analysis of both the pericellular and cytoplasmic *** addition,treatment of the cultures with exogenous proheparanase triggered co-internalization of both cell-surface HS and AMPA *** use of calcium-imaging technique,proheparanase treatment was found to reduce glutamate-induced calcium influx of the hippocampal neurons in *** with these findings,treatment of hippocampal slices with exogenous proheparanase resulted in declines in both basal synaptic strength and *** together,our findings indicate neuronal secretion of proheparanase to peri-synaptic HS-sites as a novel mechanism that contributes to synaptic plasticity by regulating AMPA receptor level at the synapse.

关键词： The role of proheparanase in synaptic plasticity of the hippocampus

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