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。     

突触长时程增强形成与学习记忆的相关研究

突触长时程增强(LTP)的形成与学习记忆有相似特征,将其作为记忆的一种模式加以研究,并深入探索LTP机制产生与静止突触的关系,长时程突触修饰与突触后神经细胞内Ca^2 的作用机制,学习行为后海马内出现的突触效能变化与行为学习之间的关系,以及BDNF对海马突触的LTP调节与长时记忆所涉及关于LTP的相关基因表达。     

东莨菪碱,印防己毒素对习得性长时程突触增强的影响

在大鼠条件性饮水反应的建立、消退和再建立过程中,于海马 CA_3区记录电极部位微量注射 M-胆碱受体阻断剂东莨菪碱和 GABA 受体阻断剂印防已毒素,观察其对习得性长时程突触增强的影响。结果表明,东莨菪碱有明显的抑制作用,印防已毒素则有明显的易化作用,同时相应地影响条件性行为;并发现习得性长时程突触增强的发展与变化是超前于条件性行为的发展和改变的。上述结果为进一步论证习得性长时程突触增强可能是学习和记忆的神经基础之一提供了证据,并提示海马 CA_3区习得性长时程增强的产生与保持有胆碱受体与 GABA 受体参与。     

蛋白激酶A参与诱导新生小鼠海马神经元的长时程增强

作为探索大脑学习和记忆功能的重要模式 ,长时程增强 (longtermpotentiation ,LTP)在研究发育过程中的神经回路形成(neuralcircuitformation)和精致化 (Refinement)具有重要作用。一般认为 ,钙 钙调蛋白依赖性蛋白激酶II(calcium/calmodulindependentproteinkinaseII ,CaMKII)和促细胞分裂剂激活性蛋白激酶 (mitogen -activatedproteinkinase,MAPK)家族分子在诱导海马神经元LTP过程中起关键作用。美国斯坦福大学学者RobertC .Malenka最近证实 :新生期啮齿类动物海马神经元却并非如此。他们于出生后 9天内的小鼠海马CA1区锥体细胞 …     

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。     

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。     

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。     

间歇性迷走神经刺激诱发的呼吸长时程增强效应

呼吸长时程增强效应(long-term facilitation,LTF)是中枢呼吸控制系统表现的一种5-羟色胺(5-HT)依赖性记忆活动,表现为间歇性低氧或窦神经刺激引起的呼吸增强效应在刺激停止后仍可持续一段时间(几分钟到几十分钟)。LTF均由吸气兴奋刺激所诱发,提示LTF的产生需要吸气神经元的兴奋性刺激,     

幼年和老年大鼠学习中海马CA_3区长时程突触增强的年龄特征

研究发现幼年和老年大鼠在条件性饮水反应的建立、消退和再建立过程中,海马CA_3区有习得性长时程突触增强(LTP)的形成、消退和再形成现象。在它的形成和再形成以及每实验日训练作业后习得性LTP的发展上,幼年鼠明显快于老年鼠,而习得性LTP的消退,在两组间无明显差异。这既表明海马CA_3区的习得性LTP具年龄特征,也为论证习得性LTP可能是学习和记忆的神经基础之一提供了新的证据。     

Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus

We measured the temporal and spatial profiles of neural precursor cells, hippocampal long-term potentiation (LTP), and signaling molecules in neurogenesis-induced adult rats. Chronic lithium treatment produced a significant 54% and 40% increase in the numbers of bromodeoxyuridine [BrdU(+)] cells after 12 h and 28 days, respectively, after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP) and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Although the number of BrdU(+) cells, approximately 90% of which were double-labeled with a neural marker neuronal nuclear protein, were markedly increased in the granule cell layer (GCL) 28 days after the completion of the 28-day lithium treatment, the magnitude of LTP observed at this time was similar to that observed 12 h after completing the 28-day lithium treatment. However, protein levels of calcium and calmodulin-dependent protein kinase II, p-Elk and TrkB were highly elevated until 28 days after the 28-day lithium treatment. Acute lithium treatment for 2 days also enhanced LTP, which was accompanied by the elevated expression of p-CREB, but not by neurogenesis. Our results suggest that the enhancement of LTP is independent of the increased number of neurons per se and it is more closely associated with key molecules, which are probably involved in neurogenesis.     

Chronic lithium enhances hippocampal long-term potentiation,but not neurogenesis,in the aged rat dentate gyrus

We investigated the hippocampal long-term potentiation (LTP), neurogenesis, and the activation of signaling molecules in the 20-month-old aged rats following chronic lithium treatment. Chronic lithium treatment produced a significant 79% increase in the numbers of BrdU(+) cells after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP), and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Our results show that as with young rats, chronic lithium can substantially increase LTP and the number of BrdU(+) cells in the aged rats. However, neurogenesis, assessed by colocalization of NeuN and BrdU, was not detected in the aged rat DG subjected to chronic lithium treatment. Therefore, it is concluded that the increase in LTP and the number of BrdU(+) cells might not be associated with increases in neurogenesis in the granule cell layer of the DG. Lithium might has a beneficial effects through other signaling pathways in the aged brain.     

Effects of Chronic Stress and Phenytoin on the Long-term Potentiation （LTP） in Rat Hippocampal CA1 Region

Stress is the response to stimulation from inside andoutside with complicated effects on organisms. Appropri-ate stressful reactions are helpful in resisting diseases byactivating unspecific modulation system, while severe orprolonged stresses are harmful and even induce mentaland physical disorders such as recurrent depression, post-traumatic stress disorder (PTSD), Alzheimer’s disease andepilepsy [1]. Hippocampus, a main brain region of keyimportance for learning, memory and emotion, is t…     

葛根素对血管性痴呆大鼠海马突触传递长时程增强的影响

目的：探讨葛根素对血管性痴呆大鼠长时程增强（LTP）的影响。方法：采用Morris水迷宫和LTP诱导法检测血管性痴呆模型大鼠空间学习记忆能力和海马突触传递的改变。结果：模型组大鼠不同时间点测得的Morris水迷宫逃逸潜伏期均较假手术组明显延长,海马LTP诱导率明显降低,而药物组大鼠EL均短于模型组,但LTP诱导率明显增强。结论：葛根素可增强血管性痴呆大鼠突触传递功能,改善其长期存在的学习记忆障碍。     

海马长时程增强与26S蛋白酶复合体活性变化的关系

实验观察了大鼠海马脑片上突触传递长时程增强(long term potentiation,LTP)的产生和维持中26S蛋白酶复合体活性的动态变化过程,初步分析了介导其变化的受体途径。结果显示:强直刺激前,26S蛋白酶复合体活性为190±14.3 cpm/(100 μg·2 h),强直刺激诱导fEPSP斜率增加10 min时,其活性升为273±18.3 epm/(100μg·2 h),强直刺激诱导fEPSP斜率增加60 min时,26S蛋白酶复合体活性又降为210±12.8 cpm/(100μg·2 h)。NMDA受体特异阻断剂AP-5在损害L1P产生的同时,抑制26S蛋白酶复合体活性升高。实验结果提示:大鼠海马LTP产生过程中,26S蛋白酶复合体活性存在一个短时间的,依赖于N-methyl-D-aspartate(NMDA)受体的升高过程。     

双电极绑定技术记录在体大鼠海马CA1区长时程增强

目的:探讨双电极绑定条件下记录大鼠在体海马CA1区长时程增强的可行性。方法:雄性Wistar大鼠乌拉坦麻醉;脑立体定位仪上埋置脑室导管;安装自制的刺激/记录绑定电极;引导基础性场兴奋性突触后电位(fEP-SP);强直刺激诱导长时程增强(LTP)。结果:绑定后的刺激和记录电极能可靠地引起海马CA1区fEPSP,fEPSP的出现率几乎100%;基础性fEPSP记录可保持长时间稳定;高频刺激成功诱导出LTP并维持达3h以上,诱导率约67%;双脉冲易化记录稳定、可靠;脑室注射β淀粉样蛋白(Aβ)对LTP显示出明显的压抑作用。结论:采用双电极绑定技术进行在体海马LTP记录简便易行、节省资源、引导fEPSP和诱导LTP的成功率较高,有望成为一项重要的研究学习和记忆机制的电生理辅助手段。     

(-)-Clausenamide potentiates synaptic transmission in the dentate gyrus of rats

The effect of clausenamide on synaptic transmission in the dentate gyrus of rats in vivo and its possible mechanism of action were investigated in this study. Four of 16 enantiomers showed potentiating effects on basal synaptic transmission in anesthetized animals. By comparing one pair of enantiomers, (-)-clausenamide and (+)-clausenamide, we can report three primary findings: (1) (-)-clausenamide potentiated synaptic transmission in both anesthetized and freely moving animals while (+)-clausenamide showed no or little effect; (2) (-)-clausenamide increased the magnitude of long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in anesthetized animals whereas (+)-clausenamide had no effect; (3) voltage-dependent calcium channels (VDCCs) calcineurin and calpain are involved in (-)-clausenamide-induced potentiation of synaptic transmission. Because hippocampal LTP is thought to reflect a cellular mechanism involved in learning and memory, our findings may provide the pharmacological basis for understanding the nootropic mechanisms of (-)-clausenamide, which is the first chiral nootropic agent developed in China.     

D-半乳糖合并Meynert基底核损毁对海马长时程增强和突触形态的影响

目的 :研究D 半乳糖合并Meynert基底核损毁Alzheimer病 (AD)大鼠模型海马突触可塑性的变化。方法 :通过0 .96 %D 半乳糖致亚急性损伤及鹅膏蕈氨酸损毁Meynert基底核建立AD动物模型 ,应用行为学测试、电生理学方法和电镜观察 ,研究AD模型大鼠海马突触形态结构和长时程增强现象 (long termpotentiation ,LTP)的变化。结果 :①AD模型大鼠在Morris水迷宫的学习记忆能力明显低于对照组 ;②AD大鼠海马CA1区突触的数密度、面密度明显减少 ;③AD模型大鼠海马齿状回产生的LTP较对照组明显降低。结论 :海马突触结构改变和功能可塑性的降低可能与AD大鼠的学习记忆能力下降有关