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Effects Of PNS On Synaptic Transmission Of Rat Hippocampal CA1 Region And Its Mechanisms

Posted on:2008-10-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhouFull Text:PDF
GTID:1114360218456371Subject:Pharmacology
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PartⅠEffects of PNS on CA1 afferent fiber-evoked postsynaptic currents in hippocampal slices of ratsObjective:To investigate the effects of Panax notoginseng saponins(PNS)on both the excitatory and inhibitory synaptic transmission in the pyramidal neurons in hippocampal CA1 region.Methods:Wistar male rats(3~4W)were killed by cervical dislocation and hippocampal slices(400μm)were prepared,blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in hippocampal slices to examine and analyze the effects of PNS(0.05~0.4 g·L-1)on CA1 afferent fiber-evoked excitatory postsynaptic currents(EPSCs)and inhibitory postsynaptic currents(IPSCs),respectively.Moreover,the Schaffer collateral/commissural pathway was stimulated with paired pulses(interpulse interval was 50 ms)and the paired-pulse facilitation(PPF)was analyzed by EPSC2 / EPSC1 ratio.Results:0.1~0.4 g·L-1PNS significantly depressed amplitude of EPSCs in neurons in the hippocampal CA1 region(p<0.05).The EPSC2/EPSC1 ratio was markedly increased after PNS application(p<0.05).But amplitude of IPSCs had no significant changes(P>0.05).Conclusion:The inhibitory effect of PNS on EPSCs in hippocampal CA1 pyramidal neurons is not due to the reinforcement of the inhibiting interneurons.It may be a result of direct inhibition on excitatory synaptic transmission.EPSC2/ EPSC1 ratio was increased after PNS application is suggested that PNS depress excitatory synaptic transmission by presynaptic mechanism. PartⅡEffects of PNS on long-term potentiation of rat hippocampal CA1 regionAim:Investigate the effects of Panax notoginseng saponins(PNS)on long-term potentiation(LTP)in CA1 region pyramidal neurons of rat hippocampal slices and analyse the cell electrophysiological mechanism underlying the potentiation of learning and memory by PNS.Methods:Wistar rats(3~4W)were killed by cervical dislocation and hippocampal slices(400μm)were prepared,blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in hippocampal slices to examine and analyze the effects of PNS on CA1 afferent fiber-evoked excitatory postsynaptic currents(EPSCs).Moreover,the Schaffer collateral/commissural pathway was stimulated by high frequent stimulation(HFS:100 Hz)pulses and effects of PNS on LTP was analyzed.Results:Amplitude of EPSCs had no significant changes after PNS(0.04~0.05 g·L-1)application(p>0.05),but 0.04~0.05 g·L-1PNS significantly increased amplitude of LTP in neurons in the hippocampal CA1 region(p<0.05).Conclusion:Facilitated LTP induction of PNS in CA1 pyramidal neurons of rat hippocampal slices may contribute to the potentiation of learning and memory by PNS,and PNS could be considered as a promising antidementia drug used to treate Alzheimer's disease.PartⅢEffects of PNS on miniature excitatory post synaptic currents in hippocampal CA1 region of ratsAim:To investigate the effects of Panax notoginseng saponins(PNS)on miniature excitatory post synaptic current in the pyramidal neurons in hippocampal CA1 region of rats. Methods:Blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in hippocampal slices(400μm)of Wistar male rats(3~4W)to examine and analyze the effects of PNS(0.05~0.4 g·L-1)on miniature excitatory post synaptic current(mEPSC).Results:0.05~0.4 g·L-1PNS significantly increased the frquency of mEPSC(p<0.05),but the amplitude of mEPSC remained unchanged(P>0.05).Conclusion:PNS changed excitatory synaptic activity of hippocampal CA1 pyramidal neurons possibly by influence upon the pre-synaptic site of the neurons.The nAChRs located at the presynaptic site may be responsible for the enhancement of PNS on mEPSC frequency.And this may contribute to the cognition-enhancing effect of PNS.Summary1.The inhibitory effect of PNS on EPSCs in hippocampal CA1 pyramidal neurons is not due to the reinforcement of the inhibiting interneurons.It may be a result of direct inhibition on excitatory synaptic transmission.EPSC2/EPSC1 ratio was increased after PNS application is suggested that PNS depress excitatory synaptic transmission by presynaptic mechanism.2.Facilitated LTP induction of PNS in CA1 pyramidal neurons of rat hippocampal slices may contribute to the potentiation of learning and memory by PNS,and PNS could be considered as a promising antidementia drug used to treate Alzheimer's disease.3.PNS changed excitatory synaptic activity of hippocampal CA1 pyramidal neurons possibly by influence upon the pre-synaptic site of the neurons.The nAChRs located at the presynaptic site may be responsible for the enhancement of PNS on mEPSC frequency.And this may contribute to the cognition-enhancing effect of PNS.
Keywords/Search Tags:Panax notoginseng saponins, hippocampal CA1 region, presynaptic inhibition, excitatory postsynaptic currents, inhibitory postsynaptic currents, Hippocampal CA1 region, Long-term potentiation, high frequent stimulation, Excitatory postsynaptic currents
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