慢性应激对大鼠海马CA1区长时程增强的影响及苯妥英钠的效应

目的　探讨慢性应激对海马功能的影响及苯妥英钠对它们的效应。方法　采用离体海马脑片结合电生理的方法 ,观察慢性应激对大鼠海马CA1区长时程增强 (LTP)的作用及苯妥英钠的效应。应用群体峰电位 (PS)的幅值和场兴奋性突触后电位 (fEP SP)的斜率作为观测LTP指标。在CA3区Schaffer侧支上施加高频刺激 (HFS) ,观察CA1区PS幅值和EPSP斜率在HFS前后的变化。结果　HFS后对照组和应激加苯妥英钠组LTP形成率、PS幅值和EPSP斜率变化的幅度均明显高于应激组和应激加生理盐水组 (P <0 0 5 )。对照组和应激加苯妥英钠组上述三个指标比较则无明显差异 (P >0 0 5 )。结论　慢性应激抑制海马CA1区LTP的形成 ,而苯妥英钠使应激海马LTP的形成保持在正常状态     

慢性应激对大鼠海马CA3区长时程增强的影响

目的　探讨慢性应激对大鼠海马CA3区长时程增强 (LTP)的影响及机制。方法　将 34只Wistar大鼠随机分成应激组 (8只 )、应激 +盐水组 (8只 )、应激 +MK 80 1组 (8只 )及空白对照组 (1 0只 ) ,应激刺激为饮水冲突模型 ,分别于实验初和LTP检测前 1天评定大鼠情绪性行为 ,在应激 1 5天后检测大鼠强直性LTP ,测量强直后 1 ,5 ,1 0 ,30 ,60 ,90 ,1 2 0minLTP群体峰电位幅度及峰潜期。结果(1 )应激前各组情绪性行为评分的差异均无显著性 ;应激后 ,应激 +盐水组 [(4 33± 0 50 )分 ]、应激 +MK 80 1组 [(3 60± 0 55)分 ]及应激组 [(2 90± 0 74)分 ]的评分均高于对照组 [(2 0 2± 1 1 6)分 ] ,差异有显著性 (P =0 0 0 0 ) ;(2 )应激组测试刺激阈值较对照组高 (45V∶30V) ;(3)在强直后第 1 ,90min时的LTP群体峰电位变化率应激组 [分别为 (2 1 1± 58) %和 (2 4 3± 69) % ]、应激 +盐水组 [分别为 (1 69±92 ) %和 (1 82± 1 61 ) % ]低于对照组 [分别为 (30 2± 2 1 0 ) %和 (30 3± 1 4 1 ) % ]和应激 +MK 80 1组 [分别为(375± 99) %和 (489± 2 36) % ] ,差异有显著性 (P <0 0 5) ,应激 +MK 80 1组与对照组的差异无显著性 ;(4)各应激组于各时点LTP峰潜期均较对照组长 ,但差异未呈显著性。结论　慢性     

雌激素对卵巢切除大鼠海马长时程增强的影响

观察雌激素对卵巢切除大鼠海马齿状回长时程增强的影响。采用电生理（长时程增强）指标探讨雌激素对回巢切除大鼠海马齿状回长时程增强的影响。结果提示：卵巢切除后（3个月）,大鼠海马齿状回颗粒细胞层的群峰电位幅度（PS）明显下降,给予雌激素替代后具有明显的改善作用。由此可见,雌激素缺乏可导致海马神经突触可塑性降低。     

皮质发育障碍大鼠模型学习记忆行为和海马长时程增强的研究

目的:研究皮质发育障碍(DCD)大鼠模型空间学习记忆及离体海马长时程增强(LTP)变化,探讨DCD大鼠模型认知功能损伤的机制.方法:建立DCD大鼠模型,采用Morris水迷宫实验对DCD大鼠模型和正常对照组进行空间学习、记忆的行为学检测,应用膜片钳技术研究DCD大鼠模型海马脑片CA1区LTP的改变.结果:Morris水...     

苯妥英钠对应激鼠血清和海马NO含量的影响

目的　探讨慢性应激对大鼠血清和海马一氧化氮 (nitricoxide,NO)含量的影响及苯妥英钠对它们的效应。方法　利用强迫游泳作为应激源制作慢性应激模型 ,采用硝酸还原酶法测定各组大鼠血清和海马NO的含量。结果　对照组、应激组和应激给药组之间大鼠血清NO的含量差异无显著性 ;应激组大鼠海马NO的含量 (4 70± 15 9)nmol/g显著高于对照组 (2 34± 77)nmol/ g和应激给药组(2 0 2± 89)nmol/g (P <0 .0 1) ,后两组间的差异无显著性。结论　慢性应激对大鼠血清NO含量无影响 ,但可诱导大鼠海马NO含量升高 ,苯妥英钠可以抑制慢性应激所致海马NO的过度生成。     

应激和吗啡对不同周龄大鼠海马CA1区突触可塑性的影响

目的研究慢性应激和(或)吗啡对不同周龄Wistar大鼠海马CA1区突触可塑性的影响。方法将4周龄和10周龄(各51只)雄性Wistar大鼠分别随机分为对照组(分别为14只)、慢性应激组(分别为13只和11只)、吗啡组(分别为14只和13只)和慢性应激加吗啡组(分别为10只和13只)。以场兴奋性后电位(fEPSP)的幅值观察两个年龄段各组大鼠的突触可塑性变化。结果(1)长时程增强(LTP)：对照组、慢性应激组和吗啡组均为10周龄鼠大于4周龄鼠(P＜0.01)；慢性应激削弱了4周龄和10周龄大鼠LTP[分别为(106.8±0.3)%,(115.6±0.2)％]；吗啡易化了10周龄大鼠的LTP(135.7±0.4)%,却削弱了4周龄大鼠的LTP(105.0±0.2)%；慢性应激加吗啡组削弱了10周龄大鼠的LTP(116.7±0.3)%,却易化了4周龄的LTP(117.7±0.5)%,均P＜0.05。(2)长时程抑制(LTD)：慢性应激后10周龄大鼠不能诱导出LTD(103.9±0.3)%,却易化4周龄大鼠的LTD(88.6±0.3)%；吗啡对10周龄和4周龄大鼠的LTD均起易化作用[分别为(77.5±0.2)%,(86.4±0.5)%]；10周龄慢性应激的大鼠使用吗啡后不能诱导出LTD(110.4±0.3)%,但对4周龄大鼠的LTD起易化作用(79.1±0.2)%,均P＜0.05。结论慢性应激和(或)急性吗啡暴露分别对4周龄与10周龄大鼠海马CA1区的LTP和LTD有不同作用,存在明显的年龄差异。     

孕期及哺乳期缺锌饲喂对仔鼠学习能力及海马长时程增强的影响

探讨了小鼠孕期和哺乳期饲喂轻度缺锌饲料对仔鼠学习记忆能力的影响．实验动物为成年雌性ICR小鼠30只及其所产的仔鼠30只．怀孕母鼠随机分为3组：（A）对照组；（B）孕期及哺乳期轻度缺锌组及（C）孕期轻度缺锌组．对照饲料及轻度缺锌饲料的锌含量分别为100mgZn／kg和5mgZn／kg。A组小鼠饲喂对照饲料；B组小鼠孕期及哺乳期皆饲喂轻度缺锌饲料，而C组孕期饲喂缺锌饲料、哺乳期饲唱对照饲料．断奶后（出生第20天后）仔鼠饲喂对照饲料。70日龄（P70）后分别在穿梭箱内测试备组仔鼠的学习能力。行为测试则采用条件性回避反应模型。实验结果表明，BRC组仔鼠达到学会标准所需次数分别为45．0±5．9（n＝7）和41．7±4．8（n＝12），明显多于A组（34．7±3．9，n＝11），而B组与C组间无显著性差异。行为实验结束后，在A组和B组仔鼠的海马脑片上进行了诱导长时程增强（LTP）的实验，B组脑片上诱导的LTP明显低于A组。结果提示：孕期及哺乳期锌缺乏可造成学习能力的下降，同时也影响海马的突触可塑性，而孕期可能是锌缺乏造成这种脑功能损伤的关键时期．     

发育期大鼠海马氨基酸类神经递质的研究

目的用高效液相色谱法检测大鼠海马组织中氨基酸类神经递质,研究它们在发育期大鼠海马中含量的变化.方法采用安捷伦反相高效液相色谱柱(ZORBAX,XDB,C18,4.6mm×250mm,5μm,Agilent),异硫氰酸苯酯为柱前衍生剂,在柱温38℃下采用二元梯度洗脱,于254 nm波长处用VARIAN-Prostar 325紫外检测器和LC-WORKSTATION-V6.2色谱数据处理系统检测和处理对照品和大鼠海马样品的氨基酸色谱数据,并计算乳鼠、幼鼠和成鼠海马氨基酸含量.结果氨基酸含量在Asp0.036～0.586 mg/ml、Glu0.027～0.4336 mg/ml、Gly0.053～0.8438 mg/ml、Tau0.039～0.6312 mg/ml和GABA0.0268～0.4288 mg/ml时,其峰面积与氨基酸含量的线性相关系数均大于0.9995;五种氨基酸回收率在96.0%～106%之间.三组样品间五种氨基酸含量的差别均有极显著性意义(P<0.01).结论该法检测大鼠海马组织中氨基酸类神经递质灵敏,特异性好,且分析时间短.氨基酸类神经递质含量随大鼠海马的发育而增高.     

利培酮和氯氮平对鼠脑海马切片长时程增强的研究

为了解利培酮和氯氮平对学习与记忆的影响 ,我们对大鼠脑海马记忆长时程增强 (ＬＴＰ)现象进行研究。材料和方法　 (1)实验动物 :随机选取 10～ 15天龄、体重 15～ 2 5ｇ的Ｓｐｒｕｇｕｅ Ｄａｗｌｅｙ(ＳＤ)大鼠进行实验 ,雌雄不拘 ,共 77只。每天给其中 2 7只大鼠腹腔注射 0 0 2ｍｇ/ｍｌ的利培酮溶液 (利培酮粉由比利时杨森公司提供 ) 1ｍｌ(利培酮组 ) ,给 2 5只大鼠腹腔注射 0 0 2ｍｇ/ｍｌ的氯氮平溶液 (氯氮平粉由湖南洞庭制药厂提供 ) 1ｍｌ(氯氮平组 ) ,给 2 5只大鼠腹腔注射生理盐水 (对照组 ) 1ｍｌ/ｄ ;均注射 7天 ,然后断头…     

慢性应激对大鼠海马CA3区锥体细胞形态结构的效应

目的　探讨慢性应激对大鼠海马CA3区锥体细胞形态结构的效应。方法　将 2 6只雄性Sprague Dawley大鼠随机分为对照组和应激组 ,每组 13只。采用尼氏 (Nissl)染色法、高尔基 (Golgi)镀染法和透射电镜技术 ,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞形态结构的效应。结果应激组大鼠海马CA3区锥体细胞数 (35 1± 3 9)较对照组 (38 7± 3 5 )明显减少 (P <0 0 5 ) ;顶树突的总长度为 (15 5 7± 33 3) μm ,较对照组 (195 6± 34 6 ) μm明显缩短 (P <0 0 5 )。应激组大鼠海马CA3区锥体细胞出现超微结构的改变 ,包括细胞固缩、体积缩小、核膜皱缩、线粒体变性和粗面内质网模糊不清。结论　慢性应激可引起海马CA3区锥体细胞形态和微细结构的改变及细胞丧失。     

The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus

In hippocampal CA1 area, there are at least two forms of long-term potentiation (LTP): one is N-methyl-D-aspartate (NMDA) receptor-dependent LTP (NMDA LTP), which is induced with a 25 Hz tetanus and blocked by 50 μM 2-amino-5-phosphonovaleric acid (APV); the other is NMDA receptor-independent LTP (VDCC LTP), which is induced by 200 Hz tetanus stimulation in the presence of APV and blocked by nifedipine, a voltage-dependent Ca⁺⁺ channel (VDCC) blocker, or by the intracellular injection of 1,2-bis(2-Aminophenoxoy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). The effects of anticonvulsant drugs phenobarbital, phenytoin, and valproic acid on both NMDA LTP and VDCC LTP were investigated in rat hippocampal slices. The results showed that 0.1 mg/ml valproic acid significantly altered baseline population spike amplitude by 34.6%, but the other drugs had no significant effect on the baseline population spike amplitude. Phenobarbital (0.025 mg/ml) potently blocked NMDA LTP and inhibited VDCC LTP. Phenytoin (0.02 mg/ml) had no effect on NMDA LTP but reduced VDCC LTP. Valproic acid did not inhibit VDCC LTP, but it abolished the expression of NMDA LTP in a similar manner as H-7, a nonspecific protein kinase C inhibitor. These data suggest that the anticonvulsant effects of these three drugs may be via different cellular mechanisms.     

Potassium-induced long-term potentiation in rat hippocampal slices

We observed that a transient increase in extracellular potassium concentration (50 mM for 40 s) was sufficient to induce long-term potentiation (LTP) of synaptic transmission in area CA1 of the hippocampal slice. Potassium-induced potentiation of the Schaffer collateral/commissural synapses demonstrated several features characteristic of tetanus-induced LTP: (1) population excitatory post-synaptic potential (EPSP) amplitudes were enhanced to a similar magnitude (on average 70% above baseline) which (2) lasted for more than 20 min; (3) induction was blocked by bath application of the specific N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphonovalerate (d-APV), and (4) was attenuated by reduction of the concentration of calcium in the extracellular medium. Induction of either potassium-induced LTP or tetanus-induced LTP occluded the subsequent expression of the other. Finally, exposure to high potassium in the absence of electrical stimulation was sufficient to induce LTP. Taken together, these data indicate that brief depolarizing stimuli other than tetanus can induce LTP. Because potassium-induced LTP is not restricted to the subset of afferents examined electrophysiologically, such a method could facilitate analyses of the biochemical events underlying both the induction and expression of LTP.     

Interferon-α inhibits long-term potentiation and unmasks a long-term depression in the rat hippocampus

Interferons (IFN) appear to have various neuromodulatory actions. Here, we characterized the actions of IFN-α on the electrophysiological properties of CA1 hippocampal neurons using intracellular recordings. Superfusion of this cytokine did not alter the resting membrane potential, cell input resistance, action potentials, nor GABA-mediated fast synaptic potentials. IFN-α inhibited glutamate-mediated excitatory postsynaptic potentials (gEPSPs) and reversed or prevented long-term potentiation (LTP) induced by high-frequency tetanic stimulation. IFN-α reduced gEPSP amplitude far below its control value. Only a short-term potentiation (STP) was observed when either IFN-α or -2-amino-5-phosphonovalerato (APV; NMDA receptor antagonist) were present during tetanic stimulation. After this STP in presence of APV, IFN-α had no effect on gEPSPs. APV had no effect on LTP when applied after tetanic stimulation and did also not prevent IFN-α effect on LTP. Genistein (a tyrosine kinase inhibitor) or heat inactivation prevented IFN-α effects. IFN-α also decreased the depolarization induced by local application of glutamate but did not modify those induced by NMDA. Similarly, IFN-α reversed the potentiation (induced by tetanic stimulation) of glutamate-induced depolarizations. IFN-α did not affect long-term depression (LTD) induced by low-frequency tetanic stimulation. In conclusion, IFN-α-induced inhibition of LTP is, at least in part, mediated by a postsynaptic effect, by tyrosine kinase activity, and by non-NMDA glutamate receptors. Inhibition of LTP by IFN-α unmasks LTD which is induced by the same high-frequency tetanic stimulation.     

Acute and chronic nicotine exposure reverse age-related declines in the induction of long-term potentiation in the rat hippocampus

Long-term potentiation (LTP) is widely considered to be the cellular substrate of learning and memory. The induction of LTP becomes more difficult with age in parallel with declining learning and memory ability. Because nicotine improves learning and memory in aged rats, we examined the effects of acute and chronic nicotine exposure on age-related declines in LTP induction. We found that acute nicotine exposure lowered the threshold for LTP induction in the aging hippocampus. The effect of nicotine was mimicked by the alpha7 nicotinic acetylcholine receptor (nAChR) antagonist methyllycaconitine and blocked by the non-alpha7 nAChR antagonist dihydro-beta-erythroidine, suggesting that both nicotine-mediated desensitization of alpha7 nAChRs and activation of non-alpha7 nAChRs contribute to the nicotine effect. The non-alpha7 nAChR agonist A85380 that facilitates the induction of LTP in the young hippocampus had no effect, however, suggesting that at least one pathway involving non-alpha7 nAChRs was altered by aging. Chronic nicotine treatment of aged rats also lowered the threshold for LTP induction and acute nicotine exposure lowered the threshold further in the chronic-nicotine-treated aged hippocampus. These results not only suggest that the mechanisms mediated by acute and chronic nicotine exposure are different, but also demonstrate that age-associated declines in LTP induction can be reversed with nicotine treatment.     

Thermal effects on long-term potentiation in the hamster hippocampus

Extracellular CA1 pyramidal cell activity was measured at different temperatures in hippocampal slices from the Syrian hamster (Mesocricetus auratus), a hibernator. Control records taken before and after tetanic stimulation of Schaffer collateral/commissural pathways were compared to determine if long-term potentiation (LTP) was established. LTP (an enhancement of the population spike amplitude or population synaptic response following tetanus) was elicited in slices at temperatures above 22 °C, but not in slices at temperatures of 20 °C. When LTP was established at temperatures above 24 °C, however, lowering the temperature to 20 °C did not abolish the LTP. Furthermore, when a tetanus was delivered at 20 °C and the bath temperature was then raised above 22 °C, LTP was established. These results for step changes in temperature suggest that the sequence of cellular mechanisms leading to LTP is activated, but then arrested in slices maintained at a constant temperature of 20 °C. Assuming this type of activity in the slice parallels in vivo hippocampal activity, it follows that the ability to elicit LTP in CA1 hippocampal pyramidal cells is lost when the core temperature of an animal entering hibernation falls to 20 °C.     

Serotonin inhibits induction of long-term potentiation at commissural synapses in hippocampus

This study tests the effect of serotonin (5-HT) (1 μM) on the induction of long-term potentiation (LTP) at the commissural/associational (C/A)-CA3 synapse. The C/A input to CA3 was measured by field potentials in rat hippocampal slices. At the concentrations used 5-HT had little or no effect on synaptic transmission, but suppressed the induction of LTP. Similar results were observed in normal saline and in saline containing picrotoxin (10 μM) and bicuculline (10 μM) to block GABA_A inhibition. Perfusion with methylsergide (1 μM), a 5-HT antagonist, had no effect on synaptic transmission, but partially blocked the effect of 5-HT on LTP. The block of LTP by 5-HT could be overcome by using a higher intensity of stimulation suggesting that 5-HT might hyperpolarize the postsynaptic neurons to inhibit LTP induction. We conclude that the activation of serotonergic receptors inhibits the induction of LTP at the C/A-CA3 synapse.     

Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats

The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED₅₀) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.     

The effect of repetitive transcranial magnetic stimulation on long-term potentiation in rat hippocampus depends on stimulus intensity

We investigated the effect of repetitive transcranial magnetic stimulation (rTMS) on long-term potentiation (LTP) in the rat hippocampus. Rats were magnetically stimulated at a rate of 1000 pulses/day for 7 days by a round coil, in which the peak magnetic fields at the center of the coil were 0.75 and 1.00 T. LTP enhancement was observed only in the 0.75-T rTMS group, while no change was observed in the 1.00-T rTMS group. These results suggest that the effect of rTMS on LTP depends on the stimulus intensity.     

Developmental changes in long-term potentiation in CA1 of rat hippocampal slices

Long-term potentiation (LTP) was examined in the CA1 region of rat hippocampal slices at postnatal day 9 (P9), P15, P30, P60, P90, P120, and P300. A single 100 Hz × 1 sec tetanus failed to induce LTP in P9 slices, while similar degrees of LTP were observed at P15, P30, and P60. At P30, changes in population spike (PS) amplitudes were accurately predicted by changes in dendritic excitatory postsynaptic potentials (EPSPs). However, at P15, the predicted increase in PS calculated from corresponding changes in dendritic EPSPs was significantly less than the observed increase, suggesting that EPSP-PS dissociation (ES-dissociation) plays a substantial role in LTP at P15. Additionally, the corresponding changes in somatic EPSP height measured in the CA1 cell layer did not predict the E-S dissociation at P15, suggesting that the E-S dissociation arises largely from changes in the excitability of the soma. Using a single 100 Hz × 1 sec tetanus, LTP proved difficult to induce in slices from rats ≥ P90, with slices showing initial enhancement that faded over 60 min of monitoring. © 1995 Wiley-Liss, Inc.