大鼠海马CA3区的习得性长时程突触增强

本实验应用慢性埋植电极技术以电生理学结合行为学的方法,观察大鼠条件性饮水反应的建立、消退和再建立过程中,其海马CA_3区突触效应的变化规律。以刺激内嗅区的穿通纤维(PP)诱发的单突触的群体锋电位(PS)及群体兴奋性突触后电位(EPSPs)为指标,经叠加处理分析,发现随着条件反应的建立,海马CA_3锥体细胞出现突触效应的长时程增强(LTP),它随行为反应的实验性消退而消退,而在随后再次建立条件反应时,又重新出现;且无论此LTP达最高水平还是它的完全消退均超前于条件性行为反应的水平。又在一个实验日训练作业结束时PS并未立即随之增大,在24h内它随时间而发展,但到第4小时已达最高水平,且条件反应率是与PS的水平相应的,对PS与EPSPs的斜率进行相关分析表明,PS的变化主要是突触传递功效的变化。上述结果表明,海马CA_3区随着行为训练有习得性LTP产生。从其发神变化特点及其与条件性行为的关系,提示此习得性LTP极其可能是本实验中学习和记忆的展经基础。     

在体大鼠海马Schaffer-CA1条件化双通路与海马组合突触可塑性

在戊巴比妥钠麻醉的Sprague-Dawley大鼠上,运用海马Schaffer-CA1双通路条件化作用(低频配对,600对脉冲,5Hz,配对刺激相应的兴奋性突触后电位峰值时间间隔为10ms)在两条Schaffer-CA1条件化通路上同时诱导出突触可塑性,呈现出海马组合突触可塑性。结果显示:不管海马Schaffer-CA1双通路独立与否,双通路条件化作用均可以同时诱导出长时程增强(long-term potentiation,LTP)和长时程抑制(long-term depression,LTD),呈现出LTP/LTD组合突触可塑性。结果表明:海马Schaffer-CA1双通路技术,可实现海马突触可塑性的双向诱导,可塑性的方向取决于突触的自身状态。由此提示,与传统的高频诱导LTP低频诱导LTD相比,在海马Schaffer-CA1双通路条件化作用诱导出的组合突触可塑性可以更好地编码海马相关的学习记忆,体现了海马突触可塑性的灵活性与稳定性。     

皮质酮对大鼠海马脑片CA1区长时程增强效应的影响

目的：探讨糖皮质激素对海马神经突触可塑性的影响。方法：高浓度（10^-5mol/L)皮质酮直接作用于大鼠海马脑片,记录CA1区LTP）。结果：海马脑片CA1区LTP的形成受到抑制。结论：应激时过量糖皮质激素会直接影响海马神经突触可塑性。     

寡聚体Aβ1-42对大鼠海马突触可塑性的慢性影响

突触传递的长时程抑制(long-term depression,LTD)和长时程增强(longterm-potentiation,LTP)是突触可塑性的两种重要形式,并且与学习记忆密切相关.本文探讨Sprague-Dawley(SD)大鼠在海马齿状回区(dentate gyrus,DG)注射36 h孵育形成的寡聚体Aβ...     

慢性应激对大鼠学习记忆能力和海马LTP的影响

目的和方法：本研究采用一种多因素的２１ｄ慢性应激动物模型,以Ｙ迷宫和ＬＴＰ为指标,探讨慢性应激对运动学习记忆能力和海马神经突触可塑性的影响。结果：长期慢性应激使大鼠空间学习记忆能力下降,而且,使中枢海马齿状回ＬＴＰ的诱生受到抑制。结论：慢性应激可能使大鼠海马齿状回神经突触可塑性降低,并进一步影响到学习记忆的功能。     

噪声对幼年和老年大鼠海马CA_3区习得性长时程突触增强的影响

经强噪声重复暴露(96 dB,2h/d,25 d)后,幼年和老年大鼠在条件反应的建立和再建立过程中,其海马CA_3区习得性长时程突触增强(LTP)的发展均受到明显阻抑,相应地动物达到学会标准需更多的训练。但幼年鼠受阻抑的程度更为严重。对习得性LTP的消退则在幼年和老年大鼠均无明显影响。本研究从突触功能的可塑性方面揭示幼年功物特别容易受到强噪声重复暴露的危害,提示应重视环境噪声对人类婴幼儿脑功能的损害作用的研究。     

慢性染铅对海马CA1区LTP及α-CaMKⅡ活性的抑制性影响

目的:探讨慢性染铅对海马CA1区长时程增强(LTP)及钙调素依赖性蛋白激酶Ⅱ(-αCaMKⅡ)活性的影响。方法:用同心圆电极刺激海马的Schaffer侧支,于CA1区用细胞外玻璃电极记录单脉冲刺激引起的锋电位群(PS),观察对照组及不同剂量染铅组大鼠于高频刺激(HFS)前后PS幅值的变化;同时以磷酸化抗体,用Western blots方法检测海马CA1区-αCaMKⅡ活性。结果:HFS后,对照组和低、中、高剂量染铅组的幅值分别为各自的HFS前的162.5%、105.2%、86.8%、83.0%,染铅组PS幅值变化率明显低于对照组(P<0.01);以对照组-αCaMKⅡ活性为100,则低、中和高剂量染铅组活性分别为62.0±3.7、50.8±4.0、43.3±4.1,和对照组相比P<0.01,具有显著性差异。结论:慢性染铅可抑制CA1区LTP形成,而这种抑制作用可能与铅使-αCaMKⅡ活性降低密切相关。     

发育期铅、铝共同暴露与单独铝暴露引起的大鼠海马突触可塑性损伤的差异

铝近年来被认为是一种神经毒,可以引起动物和人认知及行为的损伤。应用在位电生理技术发现慢性0,2％氯化铝暴露(从出生到成年)损伤了大鼠海马齿状回归一化群峰电位(Ps)的长时程增强(L1]P),明显降低了兴奋性突触后电位(fEPSP)LTP的去长时程增强(DP)和归一化PS LTP的DP幅度,而对fEPSP的LTP影响不大。铅是人们公认的神经毒,能造成中毒者智力、认知和行为的损伤。铅、铝作为常见的环境毒,在我们周围并存。探讨了发育期的铅、铝共同暴露和单独铝暴露所造成的突触可塑性损伤的差异。结果表明,发育期的铅、铝共同暴露明显比单独铝暴露引起的归一化PS LTP和PS LTP的DP的损伤要严重,并引起了fEPSP的LTP损伤。     

围产期慢性尼古丁摄入对子代小鼠学习与记忆的影响

尼古丁对学习记忆间接作用的研究鲜有报道。昆明小鼠母鼠受孕后随机分为对照组(CON)和尼古丁组(NIC)。CON组母鼠自由饮水,NIC组母鼠饮水中给予浓度为50μg/mL的尼古丁。子代小鼠60日龄时,进行Morris水迷宫实验,之后在体记录海马区穿通纤维通路(perforant pathway,PP)至齿状回(dentate gyrus,DG)的长时程增强(long-term potentiation,LTP)。结果显示,NIC组仔鼠的逃避潜伏期从第3天开始明显大于CON组,目标象限停留时间所占百分比和穿越平台次数均低于CON组,LTP群峰电位幅值和场兴奋性突触后电位斜率也都显著低于CON组。说明由母体摄入的尼古丁,可经胎盘和乳汁明显作用于其子代,导致子代学习记忆功能的明显损伤,其可能机制是因为海马神经元突触传递可塑性的效率显著降低。     

食物限制对鼠类生理状况的影响

食物限制对鼠类生理特征产生明显影响。限食条件下,鼠类的能量消耗下降,能量需求降低,糖类、蛋白质和脂肪等物质的代谢过程及相应的酶活性改变,细胞免疫功能降低,神经内分泌发生变化,性成熟延迟,动情周期改变,动情行为受到抑制,生殖力下降,仔代的发育受到影响,性比发生变化。现就该领域近年来的研究进展做一综述,并提出一些新的思路。     

Dynamin1 在应激致海马损伤中作用的初步探讨

Dynamin1是Dynamin 家族中的一员,它在突触囊泡的内吞和循环过程中起着重要作用,但Dynamin 1 在应激致海马损伤过程中是否发挥作用还未见报道。为了初步探讨Dynamin 1 在应激致海马损伤中的作用,分别 建立了海马应激损伤的动物模型和细胞模型来进行研究,研究结果表明,随着应激强度的增大,大鼠海马长时程增强(long-term potentiation,LTP) 效应逐渐减弱,同时通过细胞模型FM1-43 荧光染色检测到海马神经元的内吞作用也逐渐减弱,而这两个模型中Dynamin1 的表达也分别相应地下降。这些结果提示：应激过程导致了
Dynamin1 表达水平的下降,进而造成突触囊泡的内吞过程受阻,致使海马LTP效应减弱,并最终导致海马学习记忆功能衰退。     

Hippocampal Long-Term Potentiation Attenuated by Lesions in the Marginal Division of Neostriatum

The marginal division (MrD) is a spindled-neurons consisted zone at the caudal border of the neostriatum in the mammalian brain and has been verified as contributing to associative learning and declarative memory in the rat and human with behavior and functional magnetic resonance imaging methods. It was proved to have functional connections with the limbic system. Whether the MrD has influence on the hippocampal long-term potentiation (LTP) was investigated in this study. LTP was induced from the dentate gyrus (DG) in the hippocampus by high-frequency stimulation (HFS) to the perforant path (PP). The amplitude of the population spike (PS) and the slope of the excitatory postsynaptic potential (EPSP) increased significantly to form LTP in the DG of the hippocampus after HFS of PP in normal and saline-injected control groups of rats. Lesions introduced in the MrD reduced significantly both the amplitude of PS and the slope of the EPSP following HFS of the PP. The results indicated that lesions in the MrD could attenuate LTP formation in the hippocampus. Our data suggest that the MrD might very possibly have excitatory functional influence on the hippocampus and therefore might influence the function of the hippocampus.     

乌拉坦对大鼠海马CA1神经元电压门控钠通道和动作电位的作用

乌拉坦对兴奋性和抑制性配体门控通道具有广泛的可检测的作用.作者运用全细胞膜片钳技术研究乌拉坦对wistar大鼠海马CA1神经元电压门控钠通道和动作电位的作用.结果发现乌拉坦可逆并剂量依赖性地抑制钠电流和动作电位,其中,在10mmol/L浓度时可减小钠电流强度达38%,使激活曲线向去极化方向移动,并延长钠通道失活后的恢复时间,降低动作电位的幅值.这些结果表明乌拉坦对电压门控钠通道的抑制作用可能是乌拉坦全身麻醉作用的机制之一.     

Effects of A1 and A2 Adenosine Receptor Antagonists on the Induction and Reversal of Long-Term Potentiation in Guinea Pig Hippocampal Slices of CA1 Neurons

1. Using simultaneous recordings of the field EPSP and the population spike in the CA1 neurons of guinea pig hippocampal slices, we confirmed that delivery of a high-frequency stimulation (tetanus: 100 pulses at 100 Hz) produced robust long-term potentiation of synaptic efficacy (LTP) in two independent components, a synaptic component that increases field excitatory postsynaptic potentials (EPSPs) and a component that results in a larger population spike amplitude for a given EPSP size (E-S potentiation).2. In the same cells, reversal of LTP (depotentiation; DP) in the field EPSP and in the E-S component is achieved by delivering low-frequency afferent stimulation (LFS:1 Hz, 1000 pulses) 20 min after the tetanus.3. When the tetanus or LFS was applied to CA1 inputs in the presence of an adenosine A₁ receptor antagonist, 8-cyclopentyltheophylline (1 M), the field EPSP was enhances in LTP and attenuated in DP, while the E-S relationship was not significantly affected in either LTP or DP.4. When similar experiments were performed using an A₂ receptor antagonist, CP-66713 (10 M), the field EPSP was blocked in LTP but facilitated in DP, while E-S potentiation was enhanced during both LTP and DP.5. The results show that endogenous adenosine, acting via A₁ or A₂ receptors, modulates both the synaptic and the E-S components of the induction and reversal of LTP. Based on the results, we discuss the key issue of the contribution of these receptors to the dynamics of neuronal plasticity modification in hippocampal CA1 neurons.     

Glutamate Activates Phospholipase D in Hippocampal Slices of Newborn and Adult Rats

Abstract: Phospholipase D (PLD) is activated by many neuro-transmitters in a novel signal transduction pathway. In the present work, PLD activity was studied comparatively in hippocampal slices of newborn and adult rats. Basal PLD activity in adult rats was almost three times higher than in newborn rats. In newborn rats, L-glutamate and 1 S ,3 R -1-aminocyclopentane-1,3-dicarboxylic acid (1 S ,3 R -ACPD) time- and concentrationdependently enhanced the formation of [³H]phosphatidylpropanol ([³H]PP) and of [³H]phosphatidic acid in the presence of 2% propanol. N -MethylD-aspartate and kainate (both 1 m M ) caused small, but significant increases (∼50%). whereas α-amino-3-hydroxy-5-methylisoxazole-4-propionate (100 μ M ) was ineffective. Maximally effective concentrations of glutamate (1 m M ) and of 1 S ,3 R -ACPD (300 μ M ) increased the PLD activity to almost 300% of basal activity; the EC₅₀ values were 199 and 47 μ M , respectively. Glutamate receptor antagonists, such as DL-2-amino-3-phosphonopropionic acid (AP3). DL-2-aminc-5-phosphonovalenic acid, and kynurenate (all 1 m M ) did not inhibit the glutamate-evoked increase of PP formation. In slices of adult rats, the response to 1 S ,3 R -ACPD was significant, but small, whereas glutamate was effective only in the presence of the glutamate uptake inhibitor L-aspartate-β-hydroxarnate. It is concluded that glutamate activates PLD in rat hippocampus through an AP3-resistant metabotropic receptor. This effect is subject to ontogenetic development, with one important factor being glutamate uptake.     

Autoreceptor Regulation of Glutamate and Aspartate Release from Slices of the Hippocampal CA1 Area

Slices of hippocampal area CA1 were employed to test the hypothesis that the release of glutamate and aspartate is regulated by the activation of excitatory amino acid autoreceptors. In the absence of added Mg2+, N-methyl-D-aspartate (NMDA)-receptor antagonists depressed the release of glutamate, aspartate, and gamma-aminobutyrate evoked by 50 mM K+. Conversely, the agonist NMDA selectively enhanced the release of aspartate. The latter action was observed, however, only when the K+ stimulus was reduced to 30 mM. Actions of the competitive antagonists 3-[(+/- )-2-carboxypiperazin-4-yl]-propyl-l-phosphonic acid (CPP) and D-2-amino-5-phosphonovalerate (D-AP5) differed, in that the addition of either 1.2 mM Mg2+ or 0.1 microM tetrodotoxin to the superfusion medium abolished the depressant effect of CPP without diminishing the effect of D-AP5. These results suggest that the activation of NMDA receptors by endogenous glutamate and aspartate enhances the subsequent release of these amino acids. The cellular mechanism may involve Ca2+ influx through presynaptic NMDA receptor channels or liberation of a diffusible neuromodulator linked to the activation of postsynaptic NMDA receptors. (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, a selective quisqualate receptor agonist, and kainate, an agonist active at both kainate and quisqualate receptors, selectively depressed the K(+)-evoked release of aspartate. Conversely, 6-cyano-7-nitro-quinoxaline-2,3-dione, an antagonist active at both quisqualate and kainate receptors, selectively enhanced aspartate release. These results suggest that glutamate can negatively modulate the release of aspartate by activating autoreceptors of the quisqualate, and possibly also of the kainate, type. Thus, the activation of excitatory amino acid receptors has both presynaptic and postsynaptic effects.     

食物限制对异性大仓鼠气味选择的影响

通过Y型迷宫实验 ,以巢垫物为气味选择源 ,研究了大仓鼠对 60 %限食异性鼠和对照异性鼠气味选择的偏好。结果表明 ,雌雄大仓鼠均较多地选择对照异性鼠的气味 ,但这种选择上的差异并不显著(P >0 0 5 )。12 5I放射免疫法对实验鼠血清中睾酮 (雄性 )和雌二醇 (雌性 )含量的测定结果表明 ,对照鼠血清中睾酮 (雄性 )和雌二醇 (雌性 )激素与 60 %限食鼠无显著差异。表明 60 %限食对大仓鼠异性间气味选择的影响较小。