烟碱在大鼠海马诱导LTP的作用

目的　观察了烟碱在大鼠海马诱导长时程增强（ＬＴＰ） 的作用。方法　采用大鼠海马离体脑片灌流技术。结果　烟碱在大鼠海马ＣＡ１ 区可以诱发ＬＴＰ的作用;六烃季氨（Ｃ６） 可以阻断烟碱诱导ＬＴＰ;Ａｔｒｏｐｉｎｅ 对烟碱诱导ＬＴＰ作用无明显影响。无论在强直刺激前或后加入烟碱, 烟碱均可以易化强直刺激诱导ＬＴＰ的效应。结论　在大鼠海马ＣＡ１ 区烟碱可直接诱导ＬＴＰ,该作用由烟碱受体介导。烟碱可易化强直刺激诱导ＬＴＰ作用,提示两者诱导海马ＬＴＰ 的机制并不相同     

铝暴露对海马LTP及PKC生物活力的影响

学习记忆能力是人类思维活动的基本环节,对人类智慧的形成、意识的产生、知识的积累和科学文化的发展都起着关键的作用,因此,对学习与记忆的研究已成为当今神经科学的热点问题之一。海马是学习记忆的关键部位之一,其突触传递长时程增强(long-termpotentiation,LTP)是研究学习记     

刺五加皂甙对大鼠海马脑片长时程增强效应的影响

目的 探讨刺五加皂甙对大鼠海马脑片长时程增强效应(LTP)的影响。方法采用高频电刺激离体海马脑片诱导LTP,通过顺向群峰电位波幅相对增长率、峰潜伏期相对缩短率二项指标,观察刺五加皂甙对LTP的影响。结果1．25～5mg／100ml的刺五加皂甙对大鼠海马脑片LTP均有明显易化作用,研究组顺向群峰电位的波幅相对增长率和峰潜伏期的相对缩短率均比未加用刺五加皂甙对照组明显增高。结论 刺五加皂甙对大鼠海马脑片LTP有明显促进作用,表明其可提高大脑学习、记忆能力。     

刺五加皂甙对青霉素致痫后大鼠海马LTP的影响

目的研究刺五加皂甙（ASS）对青霉素致痫后大鼠海马长时程增强（LTP）的影响。方法实验分为侧脑室注射（icv）和腹腔注射（ip）两部分,每部分有NS对照组、模型对照组（青霉素致痫组）、ASS小、中、大剂量组。观察不同组别海马CA1区群峰电位（PS）幅度的差异,以此探讨ASS对癫痫大鼠海马LTP的作用。结果模型对照组海马PS幅度显著小于NS对照组（P〈0.01或P〈0.05）;ASS侧脑室及腹腔注射组PS幅度显著大于模型对照组（P〈0.05或P〈0.01）;ASS（icv）中剂量组PS幅度比小、大剂量组大（P〈0.01）,小、大剂量组之间无差异;ASS（ip）小、大剂量组之间无差异。结论ASS（icv）对青霉素致痫大鼠海马LTP抑制有明显改善作用,但大剂量ASS改善作用减弱;ASS（ip）对大鼠海马LTP抑制有改善作用,但可能由于血脑屏障的存在,无量效关系。     

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。     

睡眠剥夺对记忆功能的影响机制及药物干预研究进展

睡眠剥夺(sleep deprivation,SD)对机体记忆的影响可通过多种机制实现.海马的突触可塑性是研究学习记忆机制的重要目标,长时程增强(long-term potentiation,LTP)和长时程抑制(long-termdepression,LTD)是突触可塑性重要的功能指标,因而与SD造成的记忆损伤有关.     

大黄酚对Aβ_(25-35)所致AD大鼠学习记忆及LTP的影响

目的研究大黄酚对Aβ25-35所致AD大鼠学习记忆障碍的作用及对AD大鼠海马齿状回(DG)突触传递活动的影响。方法将Aβ25-35在脑立体定位仪下注入大鼠侧脑室建立大鼠AD模型,连续给予不同剂量大黄酚(0.350,0.070,0.014 mg.kg-1,ip),采用Morris水迷宫方法和在体细胞外记录LTP的电生理学方法,观察大黄酚对AD大鼠空间学习记忆障碍的作用及对大鼠海马DG高频刺激(HFS)诱导LTP的影响。结果大黄酚(0.350,0.070,0.014 mg.kg-1,ip)可剂量依赖性地缩短AD大鼠寻找站台的时间,并对AD大鼠海马DG HFS诱导的LTP有增强作用。结论大黄酚可改善Aβ25-35所致AD大鼠学习记忆障碍并增强其海马DGHFS所诱导的LTP。     

蛇床子素对脑缺血/再灌注大鼠海马LTP及氨基酸含量的影响

目的研究蛇床子素对脑缺血/再灌注大鼠海马齿状回突触传递活动及海马内氨基酸含量的影响。方法 SD大鼠随机分为正常组、假手术组、模型组、蛇床子素组(25.0、12.5 mg.kg-1)和尼莫地平组(1.0 mg.kg-1),腔内线栓法制作右侧大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,缺血后2 h再灌。采用2,3,5-氯化三苯基四氮唑(TTC)染色法记录大鼠脑梗死体积、Morris水迷宫法观察大鼠空间学习记忆能力、电生理学方法记录中枢突触传递长时程增强(long-term potentiation,LTP)现象、高效液相色谱法记录大鼠海马内氨基酸含量的变化。结果蛇床子素(25.0、12.5 mg.kg-1,ip)可减少大鼠脑梗死体积,剂量依赖性地缩短大鼠寻找站台的时间,增强大鼠海马齿状回高频刺激(high frequency stimulation,HFS)诱导的LTP,降低再灌后72 h内海马内谷氨酸含量,蛇床子素(25.0 mg.kg-1)对于γ-氨基丁酸产生先降低后升高的调节作用,与尼莫地平组作用结果一致。结论蛇床子素改善学习记忆障碍、增强脑缺血/再灌注大鼠海马齿状回HFS诱导的LTP的作用,与调节海马内谷氨酸、γ-氨基丁酸水平有关。     

氯氮平对家兔海马齿状回突触传递及神经递质释放的影响

目的：观察给予氯氮平前后齿状回反应及细胞外多巴胺（DA）和5-羟色胺（5-HT）水平的变化规律。方法：15只成年家兔,将刺激用微电极置于海马穿通纤维处,记录用微电极和收集神经递质的引导插管置于同侧齿状回处,经10d康复后随机分为对照组（C组）、强直刺激组（T组）和无强直刺激组（N组）,每组各5只。整个实验180min,分3阶段（60min/阶段）。全程给予齿状回单极方脉冲电刺激,60min时分别腹腔注射20mg/kg氯氮平溶液（T组和N组）或空白溶剂（C组）,120min时给予强直刺激（C组和T组）。实验中,每隔2min记录一次齿状回反应,每隔5min检测一次齿状回细胞外DA和5-HT的水平。结果：齿状回反应：C组1、2阶段无改变（P〉0.05）,3阶段较1、2阶段增强（P=0.02）,产生长时程增强（LTP）;T组2阶段较1阶段增强（氯氮平增强）（P=0.004）,3阶段较2阶段进一步增强（P=0.02）,产生LTP;N组2阶段较1阶段增强（氯氮平增强）（P=0.004）,3阶段同2阶段（P〉0.05）。细胞外DA和5-HT的水平：C组的DA水平在3个阶段均无改变（P〉0.05）;T组2、3阶段DA水平较1阶段明显升高（P〈0.01）,但3阶段的DA水平却没有因LTP的产生而出现相应的改变;N组2、3阶段DA水平较1阶段明显升高（P〈0.01）;3组在全部实验中的5-HT水平均无改变（P〉0.05）。结论：氯氮平可在齿状回同步产生氯氮平增强和细胞外DA水平的增加。     

吗啡依赖大鼠视皮层GABA及分解代谢酶的变化

目的通过对吗啡依赖大鼠视皮层γ-氨基丁酸(GABA)含量及GAD与GABA-T活力的测定,研究吗啡成瘾过程中视皮层γ-氨基丁酸的代谢变化。方法30只SD大鼠分为6组,末次给药前10 min,后10 min,后3 h处死组及相应对照组,每组5只。纸电泳法检测各组大鼠视皮层中GABA含量,分光光度法检测GAD与GABA-T的活力。结果吗啡末次给药前处死组大鼠GABA含量(0.09±0.03)μmol/mg与对照组(0.17±0.05)μmol/mg比较,差异有统计学意义,末次给药后处死组GABA含量回复至对照组水平。结论吗啡依赖形成时视皮层处于去抑制状态。     

妊娠期接触酒精对子鼠视皮质神经元数量的影响

目的探讨酒精对C57BL/6小鼠胚胎发育和视皮质神经元数量的的影响。方法妊娠母鼠酒精灌胃直至小鼠出生;采用苏木精-伊红和Nissl染色法观察P0、P7和P14小鼠视皮质神经元密度(ND)和皮层的厚度(CCT)。结果酒精组出现死胎和畸形。晚期胚胎和新生鼠发现多种畸形,如:小头畸形、无脑儿、脊柱脊髓裂等,畸形的出现率为12%。酒精组视皮质的发育明显滞后于对照组,皮质的分层和神经元的极性紊乱。在酒精实验组出现神经元的缺失。在各年龄组,酒精组视皮质神经元的密度均明显低于对照组(P<0.01),而酒精实验组应见皮质的厚度明显比对照组薄(P<0.01)。结论出生前酒精处理诱导视皮质神经元的缺失,此作用具有剂量依赖性和长时程性效应。     

Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on long-term potentiation and [3H]MK-801 binding in occipital cortex and hippocampus.

The central nervous system is one of the target organs for polychlorinated biphenyls (PCBs). We measured the effects of maternal exposure of Long-Evans rats to a mixture of PCB congeners reconstituted according to the pattern found in human breast milk (reconstituted mixture, RM) on long-term potentiation (LTP) in two brain regions. Exposure of the dams via food started 50 days prior to mating and was terminated at birth. In the first experiment, adult male and female offspring were exposed maternally to 40 mg/kg of the RM or the commercial mixture Aroclor 1254 (A1254). LTP and paired-pulse inhibition were measured in slices of the visual cortex. In addition, the binding of [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel as well as the [3H]muscimol binding to the GABA-A receptor in membrane preparations from the occipital cortex and hippocampus were determined. LTP as well as [3H]MK-801 binding were significantly reduced in the cortex following PCB exposure, while [3H]MK-801 binding in the hippocampus was not affected. In a succeeding experiment, LTP was determined in cortical and hippocampal slices from rats at postnatal days 10 to 20, following exposure to 0, 5, or 40 mg/kg of the RM. Cortical LTP was significantly affected by the RM while no effects were seen in hippocampal LTP. Taking the two experiments together, PCB exposure significantly reduced LTP, as well as [3H]MK-801 binding, in the cortex and had no effect in the hippocampus. The LTP deficits can only partly be related to the reduction of binding sites to the NMDA receptor; other PCB-induced neurochemical changes have to be assumed.     

Effects of nicotine on levels of acetylcholine and biogenic amines in rat cortex

Transcortical dialysis was employed to investigate the effects of systemic nicotine (3.6 μmol/kg, sc) administration on cortical extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT). Systemic administration of [–]-nicotine produced a 106% increase of cortical ACh release over basal levels that persisted for approximately 2 h. Concurrently, NE levels were increased 86% over basal values for 60 min. The effects appear to be stereoselective, as systemic injections of [+]-nicotine significantly increased cortical ACh levels only 48% over basal levels for 30 min, and NE levels in the dialysate only 43% over control levels for 60 min. No significant changes of basal dopamine (DA) or serotonin (5-HT) levels were observed, although DA did appear to increase in response to systemic nicotine. In addition, striatal total endogenous ACh increased significantly over control levels 15 min after [–]-nicotine administration (3.6 μmol/kg, sc), and then significantly declined after 3 h, suggesting that nicotine may influence synthesis as well as release. Analysis of total ACh levels in cortical tissue revealed a similar trend. At the dose utilized in this study, no changes in the cortical electroencephalogram (EEG) were observed. © 1994 Wiley-Liss, Inc.     

Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity

NMDA-type glutamate receptors (NMDARs) mediate many forms of synaptic plasticity. These tetrameric receptors consist of two obligatory NR1 subunits and two regulatory subunits, usually a combination of NR2A and NR2B. In the neonatal neocortex NR2B-containing NMDARs predominate, and sensory experience facilitates a developmental switch in which NR2A levels increase relative to NR2B. In this review, we clarify the roles of NR2 subunits in synaptic plasticity, and argue that a primary role of this shift is to control the threshold, rather than determining the direction, for modifying synaptic strength. We also discuss recent studies that illuminate the mechanisms regulating NR2 subunits, and suggest that the NR2A/NR2B ratio is regulated by multiple means, which may control the ratio both locally at individual synapses and globally in a cell-wide manner. Finally, we use the visual cortex as a model system to illustrate how activity-dependent modifications in the NR2A/NR2B ratio may contribute to the development of cortical functions.     

应用微透析技术和质谱法测定川芎嗪对大鼠脑内乙酰胆碱释放量的影响

本文结合脑内微透析技术与现代分析方法，考察川芎嗪对大鼠脑内乙酰胆碱释放的影响。采用脑内微透析技术进行取样，建立高效液相-串联四极杆质谱方法测定脑透析液中的乙酰胆碱含量。结果显示，川芎嗪皮下给药能够剂量相关地增加大鼠脑内不同脑区中乙酰胆碱的释放。该法能够准确反映药物对大鼠脑内乙酰胆碱释放量的影响，与传统方法相比，具有明显的优势。     

3,4-Methylenedioxymethamphetamine enhances the release of acetylcholine in the prefrontal cortex and dorsal hippocampus of the rat

Rationale The neurochemical effects produced by acute administration of 3,4-methylenedioxymethamphetamine (MDMA) on the monoaminergic systems in the brain are well documented; however, there has been little consideration of the potential effects of MDMA on other neurotransmitter systems. Objective The present study was designed to investigate the acute effect of MDMA on cholinergic neurons by measuring acetylcholine (ACh) release in the medial prefrontal cortex (PFC) and dorsal hippocampus, terminal regions of cholinergic projection neurons originating in the basal forebrain. Methods In vivo microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) were used to assess the effects of MDMA on the extracellular concentration of ACh in the PFC and dorsal hippocampus of the rat. Results The systemic administration of MDMA (3–20 mg/kg, i.p.) resulted in an increased extracellular concentration of ACh in the PFC and dorsal hippocampus. Reverse dialysis of MDMA (100 μM) into the PFC and hippocampus also increased ACh release in these brain regions. Treatment with parachlorophenylalanine and α-methyl-para-tyrosine, inhibitors of serotonin (5-HT) and dopamine (DA) synthesis, respectively, significantly attenuated the release of ACh stimulated by MDMA in the PFC, but not in the dorsal hippocampus. Conclusions MDMA exerts a stimulatory effect on the release of ACh in the PFC and dorsal hippocampus in vivo, possibly by mechanisms localized within these brain regions. In addition, these results suggest that the MDMA-induced release of ACh in the PFC involves both serotonergic and dopaminergic mechanisms.     

MK-801对大鼠海马长时程增强的作用

目的观察了ＭＫ ８０１对大鼠海马长时程增强的作用。方法采用大鼠海马离体脑片灌流技术。结果强直刺激（１００Ｈｚ,１ｓ）在大鼠海马ＣＡ１区可以诱发ＬＴＰ的作用;在给１０μｍｏｌ·Ｌ－１ＭＫ ８０１过程中,给予强直刺激仍能诱导ＬＴＰ的形成;强直刺激诱导ＬＴＰ后给予ＭＫ ８０１不能抑制ＬＴＰ的形成;在孵育槽中加入１０μｍｏｌ·Ｌ－１ＭＫ ８０１孵育２ｈ后给予强直刺激不能诱导ＬＴＰ的形成。结论预先给予ＭＫ ８０１可以阻断强直刺激诱导ＬＴＰ的形成。     

Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats

The benzodiazepine diazepam impairs memory and long-term potentiation (LTP) in the hippocampus. Here, we investigate the effect of diazepam on LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in urethane-anesthetized Sprague--Dawley rats. Diazepam was applied locally at the recording spinal segments before and after LTP induction by tetanic stimulation. We found (1) Diazepam completely blocked LTP induction. (2) Diazepam and midazolam reversed spinal LTP, when applied at 30 min after LTP induction and depressed but could not reverse spinal LTP, when applied at 3 h after LTP induction. (3) Pretreatment with benzodiazepine receptor antagonist flumazenil or GABA(A) receptor antagonist bicuculline completely blocked the inhibitory effects of diazepam on spinal LTP. In contrast, when the inhibitory effect of diazepam was fully established, neither of these antagonists was capable of reversing the inhibition by diazepam. (4) Spinal application of the GABA(A) receptor agonist 3-amino-1-propanesulfonic acid (3-APSA) at a dose of 50 microg, produced a transient inhibition of spinal LTP. These results suggest that diazepam might prevent and depress spinal plastic change produced by noxious stimulation via activation of the GABA(A) -benzodiazepine receptor complex.