石杉碱甲对大鼠海马脑片CA1神经元θ节律及长时程增强的影响

目的:研究石杉碱甲(HupA)对大鼠海马脑片CA1锥体神经元θ节律、长时程增强的影响,以分析其增强学习记忆功能的神经细胞电生理机制。方法:应用大鼠海马脑片神经元细胞内记录技术,观察石杉碱甲对大鼠海马脑片的CA1锥体神经元θ节律、长时程增强的影响。结果:(1)未用药组出现膜电位振荡前后4～10Hz(θ节律)功率分量之和无显著性差异,但在HupA(1μmol·L-1)灌流15min后出现膜电位振荡,与用药前没有膜电位振荡的4～10Hz功率分量之和配对t检验比较有显著差异(n=3,P<0.005)。(2)在LTP期间,对照组EPSP幅度在强直刺激后30min显著性的升高(P<0.05),而HupA组在强直刺激后15min即出现显著性升高(P<0.01)。结论:HupA可增加大海马锥体神经元在θ频率范围内的功率分量,并易化LTP的诱发,这可能是其增强学习记忆功能的细胞电生理机制之一。     

短暂性局部脑缺血对大鼠海马脑片突触传递长时程增强的影响

与海马区神经元活动相关的长时程增强(LTP)是学习记忆的基础。研究应用大鼠海马脑片,检测缺血(缺氧/低血糖)对高频刺激诱导的突触传递LTP的影响。方法     

石杉碱甲的研究现状

目的:介绍近几年石杉碱甲药理作用的研究进展.方法:查阅相关文献并进行综合分析.结果:石杉碱甲不仅通过抑制胆碱酯酶活性,还可以通过影响自由基系统,降低生长抑素、细胞内[Ca2 ]、谷氨酸含量,提高钙调蛋白(CaM)和钙调蛋白的信使核糖核酸(CaMmRNA)表达水平等多种药理机制,提高认知功能和学习记忆能力.结论:石杉碱甲有可能成为理想的抗衰老药物之一.     

血管性痴呆小鼠海马CA1区锥体细胞形态结构及石杉碱甲对其影响

目的:观测血管性痴呆(VD)小鼠海马CA1区锥体细胞及石杉碱甲的治疗效果.方法:制作VD动物模型,并设立假手术组、石杉碱甲组;测试学习和记忆成绩;观测海马CA1区锥体细胞及顶树突,透射电镜观察其超微结构.结果:模型组学习和记忆成绩降低(P＜0.05),且海马CA1区锥体细胞数目也降低(P＜0.05),其顶树突总长度显著...     

血管性痴呆小鼠海马神经细胞钙稳态及石杉碱甲的影响

目的观察石杉碱甲对VD小鼠海马神经细胞钙稳态的影响。方法制备VD动物模型,并设立假手术组作,选用石杉碱甲为治疗组。进行学习、记忆成绩测试,在LSCM下观察海马神经细胞静息态[Ca2+]i及其在去极化时的动态变化。结果模型组的学习和记忆成绩低于假手术组及治疗组;而模型组静息态[Ca2+]i显著高于假手术组、治疗组,并且海马神经细胞[Ca2+]i升高幅度明显降低,恢复时间明显延长。结论 VD小鼠海马神经细胞钙稳态变化参与了其发病机制,石杉碱甲可改善海马神经细胞钙稳态变化。     

石杉碱甲对基底核大细胞部损毁所致工作记忆障碍的影响

目的：研究石杉碱甲对基底核大细胞部（ＮＢＭ）损毁诱导的工作记忆障碍的影响。方法：采用八臂迷宫延迟板程序研究空间记忆。胆碱乙酰转移酶（ＣｈＡＴ）活力测定采用［＾３Ｈ］乙酰辅酶Ａ转变成［＾３Ｈ］乙酰胆碱的方法。结果：单侧损毁ＮＢＭ（卡因酸０．０２μｍｏｌ）导致空间记忆障碍。在不同的延迟间隔，大鼠完成程序产生的正确数减少和错误数增多。损毁侧大脑皮层ＣｈＡＴ酶的含量下降了大约４０％。石杉碱甲（０．２ｍｇ·     

石杉碱甲对AD小鼠学习记忆能力的改善

目的进一步验证石杉碱甲对学习记忆能力的改善.方法用D-半乳糖和亚硝酸钠建立的小鼠模型,通过跳台实验来检验小鼠的学习记忆能力的变化.结果模型组与空白组相比学习记忆能力显著降低,而用药组与模型组相比,学习记忆能力大大恢复.     

石杉碱甲和乙促进小鼠的空间辨别学习和记忆

石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075～0.125 mg/kg或Hup-B 0.4～0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO_2产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1～0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。     

Effects of emodin on synaptic transmission in rat hippocampal CA1 pyramidal neurons in vitro

Rhubarb extracts provide neuroprotection after brain injury, but the mechanism of this protective effect is not known. The present study tests the hypothesis that rhubarb extracts interfere with the release of glutamate by brain neurons and, therefore, reduce glutamate excitotoxicity. To this end, the effects of emodin, an anthraquinone derivative extracted from Rheum tanguticum Maxim. Ex. Balf, on the synaptic transmission of CA1 pyramidal neurons in rat hippocampus were studied in vitro. The excitatory postsynaptic potential (EPSP) was depressed by bath-application of emodin (0.3-30 microM). Paired-pulse facilitation (PPF) of the EPSP was significantly increased by emodin. The monosynaptic inhibitory postsynaptic potential (IPSP) recorded in the presence of glutamate receptor antagonists (DNQX and AP5) was not altered by emodin. Emodin decreased the frequency, but not the amplitude, of the miniature EPSP (mEPSP). The inhibition of the EPSP induced by emodin was blocked by either 8-CPT, an adenosine A1 receptor antagonist, or by adenosine deaminase. These results suggest that emodin inhibits the EPSP by decreasing the release of glutamate from Schaffer collateral/commissural terminals via the activation of adenosine A1 receptors in rat hippocampal CA1 area and that the neuroprotective effects of rhubarb extracts may result from decreased glutamate excitotoxicity.     

Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats

In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 micromol/l. DMA(V) had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA(III) significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 micromol/l DMA(III) in adult and 10 micromol/l DMA(III) in young rats. Moreover, DMA(III) significantly affected the LTP-induction. Application of 10 micromol/l DMA(III) resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA(III). In slices of young rats, the depressant effects of DMA(III) were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA(V) on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.     

Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krüger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krüger, K., Straub, H., Binding, N., Muβhoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krüger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Muβhoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA^V) and monomethylarsonous acid (MMA^III) also influence the synaptic functions of the hippocampus.In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds.MMA^V had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA^III strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 μmol/l (adult rats) and 25 μmol/l (young rats) and LTP amplitudes at concentrations of 25 μmol/l (adult rats) and 10 μmol/l (young rats), respectively. In contrast, application of 1 μmol/l MMA^III led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Krüger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501).These effects are probably not mediated by changes in cell excitability or in presynaptic glutamate release rates, since antidromically induced population spikes and paired-pulse facilitation failed to show any MMA^III effect. The impairment of the excitatory CA1 synapse is more likely caused by the action of MMA^III on postsynaptic glutamatergic receptors and may be jointly responsible for dysfunctions of cognitive effects in arsenic toxicity.     

Triethyltin exposure suppresses synaptic transmission in area CA1 of the rat hippocampal slice

To examine the effects of TET on the electrophysiology of area CA1 of hippocampus, hippocampal slices were obtained from adult hooded rats and were maintained in vitro using standard techniques. Stimulating and recording electrodes were placed in the Schaffer collaterals and CA1 pyramidal cell body layer, respectively. Following baseline measurements, slices were exposed to either 0, 1, 3, 6, or 10 μM TET in the incubating medium. Both pyramidal cell excitability and recurrent/feedforward inhibition were suppressed in a dose-dependent manner within 3 hr postexposure. The evoked population spike and population excitatory postsynaptic potential (EPSP) were suppressed significantly by 2 hr postexposure for 1 and 3 μM TET exposures, and by 45 min postexposure for 6 and 10 μM exposures. A similar dose-dependency was observed for the suppression of recurrent/feedforward inhibition in hippocampal CA1. A second procedure tested the specificity of TET effects to axonal conduction of Schaffer collaterals. Both the stimulating and recording electrode were placed in the Schaffer collaterals so that both the Schaffer collateral population fiber volley and the CA1 pyramidal cell population EPSP could be recorded. TET exposure suppressed pyramidal cell EPSPs without significantly affecting the amplitude of Schaffer collateral fiber volleys. The results support the view that acute TET exposure suppresses synaptic transmission in area CA1 of hippocampus.     

VIP enhances both pre- and postsynaptic GABAergic transmission to hippocampal interneurones leading to increased excitatory synaptic transmission to CA1 pyramidal cells

Vasoactive intestinal peptide (VIP) is present in the hippocampus in three subtypes of GABAergic interneurones, two of which innervate preferentially other interneurones, responsible for pyramidal cell inhibition. We investigated how pre- and postsynaptic modulation of GABAergic transmission (to both pyramidal cells and interneurones) by VIP could influence excitatory synaptic transmission in the CA1 area of the hippocampus. VIP (0.1-100 nM) increased [(3)H]GABA release from hippocampal synaptosomes (maximum effect at 1 nM VIP; 63.8 +/- 4.0%) but did not change [(3)H]glutamate release. VIP (0.3-30 nM) enhanced synaptic transmission in hippocampal slices (maximum effect at 1 nM VIP; field excitatory postsynaptic potentials (epsp) slope: 23.7 +/- 1.1%; population spike amplitude: 20.3 +/- 1.7%). The action on field epsp slope was fully dependent on GABAergic transmission since it was absent in the presence of picrotoxin (50 microM) plus CGP55845 (1 microM). VIP (1 nM) did not change paired-pulse facilitation but increased paired-pulse inhibition in CA1 pyramidal cells (16.0 +/- 0.9%), reinforcing the involvement of GABAergic transmission in the action of VIP. VIP (1 nM) increased muscimol-evoked inhibitory currents by 36.4 +/- 8.7% in eight out of ten CA1 interneurones in the stratum radiatum. This suggests that VIP promotes increased inhibition of interneurones that control pyramidal cells, leading to disinhibition of synaptic transmission to pyramidal cell dendrites. In conclusion, concerted pre- and postsynaptic actions of VIP lead to disinhibition of pyramidal cell dendrites causing an enhancement of synaptic transmission.     

Valproate reduced excitatory postsynaptic currents in hippocampal CA1 pyramidal neurons

Valproate (VPA) is one of the most widely used antiepileptic drugs, and it is also increasingly used for the treatment of neuropsychological disorders and neuropathic pain, as well as migraine prophylaxis. However, the underlying cellular mechanisms of VPA on the synaptic physiology remain unclear. We investigated the effects of VPA on synaptic transmission using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA1 pyramidal neurons. Perfusion with VPA, at therapeutically attainable concentrations, decreased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by Schaffer collateral stimulation, without modifying inhibitory postsynaptic currents (IPSCs). Furthermore, VPA induced a significant reduction of the non-NMDA EPSC (non-NMDA(EPSC)) component, without modifying the NMDA EPSC (NMDA(EPSC)) component. Paired pulse facilitation and EPSC variance were not significantly affected by VPA, indicating that VPA did not decrease transmitter release probability, which suggests a postsynaptic mechanism of action. We therefore conclude that VPA decreases excitatory synaptic activity through the modulation of postsynaptic non-NMDA receptors, without modifying synaptic inhibition, and that this reduction of excitation is, at least in part, responsible for the effects of VPA.     

Use-dependent effects of acute and chronic treatment with imipramine and buspirone on excitatory synaptic transmission in the rat hippocampus in vivo

Summary The effects of acute and long-term treatment with imipramine and buspirone on the responses of rat hippocampal neurones to low and high frequency electrical stimulation were compared. Whereas acute treatment with imipramine (10 mg/kg, i.p.) had no effect on synaptic responses to low frequency stimulation, chronic treatment for 14 days significantly reduced the amplitude of the field excitatory postsynaptic potential. Both acute and chronic imipramine treatment markedly reduced the amplitude of the nerve volley and excitatory postsynaptic potential evoked at high frequency stimulation rates in a use-dependent manner. Buspirone (0.5–3 mg/kg, i.p.) produced a significant reduction of the excitatory postsynaptic potential at high frequencies. This was enhanced after repeated administration of a dose of 0.5 mg/kg for 14 days. We previously reported a similar effect of buspirone at low frequency stimulation. Both compounds therefore share the ability to exert strong depressant effects on transmission in the hippocampus especially after chronic treatment. Correspondence to M. J. Rowan at the above address     

Excitatory afferents to CA3 pyramidal cells display differential sensitivity to CB1 dependent inhibition of synaptic transmission

Recent advances in immunohistochemical techniques have, contrary to earlier reports, positively identified CB1 receptors on glutamatergic terminals in the hippocampus. Further work has implicated these receptors in modulation of susceptibility to kainic acid induced seizures. Based on these results, the current study was designed to test the hypothesis that both exogenous and endogenous cannabinoids can selectively modulate glutamatergic afferents to CA3 pyramidal cells, and that such modulation is mediated by cannabinoid type 1 (CB1) receptors. Towards that end we employed either conventional or two-photon guided minimal stimulation techniques to isolate mossy fiber and/or associational/commissural (A/C) inputs to CA3 pyramidal cells. We report that bath application of WIN55,212-2 selectively inhibits minimally evoked A/C inputs to CA3 pyramidal cells, without significantly altering simultaneously recorded mossy fiber inputs. Further, we find that WIN55,212-2 mediated inhibition of A/C inputs is completely blocked by the CB1 selective antagonist AM-251 and absent in CB1^−/− animals, suggesting a dependence on CB1 receptors. Finally, we demonstrate that depolarization of CA3 pyramidal cells leads to calcium dependent release of endogenous cannabinoids that transiently inhibit A/C mediated responses, and that this effect is also sensitive to both AM-251 and the muscarinic acetylcholine receptor antagonist atropine. To our knowledge this represents the first demonstration of depolarization induced suppression of excitation in area CA3 of the hippocampus. Collectively, these results provide new information relevant to developing a thorough understanding of how ECs modulate excitatory transmission in an area that is both essential for the acquisition of new memories and intimately involved in epileptogenesis.     

Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices

1. The present study investigated the electrophysiological effects of songorine (1–100 μM), an alkaloid occurring in plants of the Aconitum genus, in rat hippocampal slices.
2. Songorine (10–100 μM) evoked a concentration-dependent increase in the amplitude of the orthodromic population spike and in the slope of the field e.p.s.p. The enhancement was long-lasting and was not reversed by up to 90 min of washout. Songorine failed to affect size and shape of the presynaptic fiber spike which represents the compound action potential of the Schaffer collaterals. This indicates that enhancement of the synaptic response is no consequence of an increased afferent excitability.
3. The antidromically evoked population spike was not affected by songorine at concentrations up to 100 μM suggesting that the enhancement of the orthodromic population spike and of the field e.p.s.p. was not due to an increase in pyramidal cell excitability.
4. The input-output curve for the postsynaptic population spike was shifted to the left implying that a presynaptic fiber spike of the same size elicited a larger postsynaptic response, indicating a decrease in threshold for generation of the population spike.
5. The songorine-evoked increase in excitability was not affected by the NMDA receptor antagonist, D-AP5. However, the effect of songorine was completely abolished by the selective dopamine D₂ receptor antagonist sulpiride (0.1 μM) as well as by haloperidol (10 μM) and was mimicked by application of the dopamine releaser, amantadine (100 mM). In contrast, the selective D₁ receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, did not block the action of songorine.
6. The results indicate that the plant alkaloid songorine enhances excitatory synaptic transmission which may be due to an agonistic action at D₂ receptors.