腺苷A1受体和NMDA受体在海马齿状回突触传递活动中的关系

目的探讨腺苷A₁受体阻断剂对海马齿状回(DG)突触传递活动的影响及其与NMDA受体的关系。方法 采用在体记录麻醉大鼠LTP的电生理学方法,观察腺苷A₁受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)与NMDA受体激动剂、阻断剂在海马DG基础突触传递活动和高频刺激诱导的LTP中作用的相关性。结果DPCPX(6 mg·L^-1,5 μL,icv)或NMDA(0.2 mg·L^-1,5 μL,icv)不影响大鼠海马DG突触传递活动,DPCPX对icv NMDA后高频刺激诱导已形成的LTP维持也无影响;预先给予DPCPX后则可显著增强NMDA的海马DG基础突触传递活动和LTP;AP₅(0.5 mg·L^-1,5 μL)阻断NMDA受体后对LTP的抑制作用不受DPCPX的影响,但预先给予DPCPX则可取消AP₅对LTP的抑制作用。结论DPCPX不影响海马DG突触传递活动,但可影响NMDA受体的效应,增强NMDA受体在海马DG突触传递活动中的作用。     

人参总皂苷对大鼠海马齿状回突触传递活动的影响

目的：研究人参总皂苷对麻醉大鼠海马齿状回(DG)突触传递活动的影响。方法：采用在体记录LTP的电生理学方法,给予不同剂量人参总皂苷(100,50,25 mg.kg^-1,ip)观察其对海马DG基础突触传递活动和LTP的影响。 结果：给予人参总皂苷10 min后可剂量依赖性增强大鼠海马DG基础突触传递活动; 在给予高频刺激(HFS)诱导出LTP后30 min,再ip上述剂量人参总皂苷,可使已形成的LTP在ip人参总皂苷后持续增强。结论：人参总皂苷ip可剂量依赖性增强海马DG基础突触传递活动和HFS所诱导的LTP。     

腺苷A1受体阻断剂对学习记忆的影响及机制分析

目的探讨腺苷A1受体阻断剂对学习记忆的影响及其与胆碱能、氨基酸能神经的关系.方法采用避暗实验、分光光度法和HPLC法,观察腺苷A1受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对东莨菪碱(Scop)、2-氨基-5-磷戊酸(AP5)致小鼠记忆障碍及脑胆碱酯酶(AChE)活性、氨基酸水平的影响.结果 DPCPX可显著改善Scop致记忆障碍,但对AP5致记忆障碍无影响;在体内外高剂量DPCPX可显著抑制小鼠脑AChE活性;DPCPX icv可显著升高小鼠脑Glu和Asp含量,降低GABA含量,使脑内Glu/GABA比值显著升高.结论腺苷A1受体特异性阻断剂DPCPX可显著改善Scop而不能改善AP5致记忆障碍,在高剂量时可影响脑AChE活性和脑氨基酸水平、升高脑内Glu/GABA比值.     

NMDA受体在皮质酮介导海马突触可塑性损伤中的作用

目的考察皮质酮(CORT)致突触可塑性损伤与N-甲基-D-天冬氨酸(NMDA)受体的关系。方法雄性C57BL/6J小鼠(7～9周龄)剥离海马切片用于长时程增强(LTP)和长时程抑制(LTD)实验;采用灌流给药的方式,观察1μmol·L~(-1)CORT和非选择性NMDA受体拮抗剂D-AP5(50μmol·L~(-1))、选择性NR2A拮抗剂PEAQX(0.2μmol·L~(-1))和TCN-201(3μmol·L~(-1))、选择性NR2B拮抗剂Ifenprodil(3μmol·L~(-1))和Ro25-6981(1μmol·L~(-1))及NMDA受体共激活剂D-丝氨酸对LTP和LTD的影响。结果与正常组小鼠相比,CORT组小鼠海马的LTP和LTD均显著损伤(P<0.01),D-AP5可显著损伤小鼠海马的LTP和LTD(P<0.01),PEAQX和TCN-201及Ifenprodil和Ro25-6981均可显著损伤小鼠海马的LTP(P<0.01),对LTD则无显著影响;而D-Serine可显著改善CORT引起的LTP和LTD损伤(P<0.01)。结论 CORT和D-AP5对海马LTP和LTD具有相似的损伤作用,且D-丝氨酸对CORT致海马LTP和LTD损伤具有显著改善作用,提示CORT可能通过抑制NMDA受体功能影响海马突触可塑性。     

激动NMDA受体甘氨酸位点可改善皮质酮致海马长时程增强损伤

目的研究N-甲基-D-天冬氨酸(NMDA)受体甘氨酸位点与皮质酮(CORT)致长时程增强(LTP)损伤之间的关系。方法应用雄性BALB/c小鼠,采用皮下注射CORT50 mg·kg~(-1)造模,60 min后进行电生理实验。NMDA受体甘氨酸位点激动剂300 nmol/只D-丝氨酸,300 nmol/只L-丝氨酸,100 nmol/只甘氨酸(侧脑室注射)和100 mg·kg~(-1)D-氨基酸氧化酶抑制剂MPC(腹腔注射)在CORT前30 min注射,1 mg·kg~(-1)NMDA受体甘氨酸位点拮抗剂L-701,324在D-丝氨酸和MPC前30 min腹腔注射。结果与正常小鼠相比,CORT可显著损伤小鼠海马的LTP(P<0.01),D-丝氨酸、L-丝氨酸、甘氨酸和MPC均可显著改善CORT引起的海马LTP损伤(P<0.01),甘氨酸位点拮抗剂L-701,324可阻断D-丝氨酸和MPC对CORT致海马LTP损伤的改善作用(P<0.01)。结论激动NMDA受体甘氨酸位点可改善CORT致海马LTP损伤,提示CORT引起的LTP损伤可能与NMDA受体功能下降相关。     

腺苷A_1受体阻断剂对大鼠海马BDNF蛋白表达及内质网的影响

目的探讨腺苷A1受体阻断对大鼠海马BDNF蛋白表达及内质网功能的影响。方法采用免疫组化技术观察腺苷A1受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对大鼠海马颗粒细胞BDNF蛋白表达的影响;采用透射电镜技术观察DPCPX对大鼠海马神经元内质网数量的影响。结果DPCPX(0.1 mg.kg-1,ip,15 d)可增加海马颗粒细胞BDNF蛋白表达阳性细胞的数目。DPCPX(0.5 mg.kg-1,ip,15 d)能增加BDNF蛋白在海马颗粒细胞的表达,使阳性细胞数目明显增加、染色加深;同时增加大鼠海马神经元中内质网的数量,使内质网密度增加。结论DPCPX可促进大鼠海马颗粒细胞内BDNF蛋白表达和诱导海马神经元内质网功能增强。     

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。     

腺苷A1受体阻断剂对学习记忆的影响及机制分析腺苷A1受体阻断剂对学习记忆的影响及机制分析

目的探讨腺苷A₁受体阻断剂对学习记忆的影响及其与胆碱能、氨基酸能神经的关系。方法采用避暗实验、分光光度法和HPLC法,观察腺苷A₁受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对东莨菪碱(Scop)、2-氨基-5-磷戊酸(AP₅)致小鼠记忆障碍及脑胆碱酯酶(AChE)活性、氨基酸水平的影响。结果DPCPX可显著改善Scop致记忆障碍,但对AP₅致记忆障碍无影响；在体内外高剂量DPCPX可显著抑制小鼠脑AChE活性；DPCPX icv可显著升高小鼠脑Glu和Asp含量,降低GABA含量,使脑内Glu/GABA比值显著升高。结论腺苷A₁受体特异性阻断剂DPCPX可显著改善Scop而不能改善AP₅致记忆障碍,在高剂量时可影响脑AChE活性和脑氨基酸水平、升高脑内Glu/GABA比值。     

锂对大鼠海马齿状回区神经元突触可塑性的影响(英文)

目的　从齿状回长时程增强效应 (LTP)方面研究锂的治疗作用机理。方法　细胞外记录离体海马脑片神经元兴奋性突触后电位 (EPSP)。结果锂可逆地增强EPSP的幅度。高频刺激 (10 0Hz ,1s)对照组大鼠海马穿通纤维 ,在海马齿状回 (DG)区记录的EPSP幅度会持续增高 ,可以诱导出明显的突触后LTP。若用 10mmol·L- 1锂处理大鼠海马脑片 ,则诱导的LTP幅度明显降低 ,但低浓度锂 (2 ,6mmol·L- 1)不影响LTP的幅度 ;10mmol·L- 1锂明显抑制海马脑片DG区的脉冲间隔 (IPI)为 5 0ms的双脉冲易化效应 (PPF) ,而低浓度锂 (2 ,6mmol·L- 1)处理则不影响PPF(IPI,5 0ms) ;在不同的细胞外钙浓度下 ,用 10mmol·L- 1锂处理过的海马脑片PPF受到的抑制程度不同。结论　锂可能通过突触前的机理来抑制海马DG区LTP的幅度 ,这种抑制效应与锂的临床治疗狂躁症及其副作用之间的关系尚需进一步的研究。     

盐酸埃他卡林对大鼠海马神经元谷氨酸受体功能及突触活动的影响

目的 :研究盐酸埃他卡林 (Ipt)对脑神经元谷氨酸受体功能及突触活动的影响。方法 :采用原代培养的大鼠海马神经元 ,应用膜片钳全细胞记录技术 ,记录Ipt对培养的海马神经元谷氨酸或天冬氨酸(NMDA)诱发电流及神经元突触后电流的影响。结果 :Ipt(1～ 1 0 0 μmol·L- 1)可浓度依赖性地对抗培养的海马神经元谷氨酸或NMDA诱发电流 ,并为ATP敏感性钾通道拮抗剂格列本脲 30 μmol·L- 1所对抗。Ipt抑制培养的海马神经元之间突触联系形成的自发兴奋性突触后电流 ,降低其发放频率 ,抑制其电流幅度 ;但对微小兴奋性突触后电流无显著性影响。结论 :Ipt可阻断脑神经元谷氨酸受体功能 ,抑制脑神经元谷氨酸的兴奋性突触传递 ,其作用与ATP敏感性钾通道相关     

一氧化氮介导麻醉大鼠人参皂苷Rg1诱发长时程增强

目的：研究人参皂苷Rg1对麻醉大鼠突触传递效能的影响及作用机制。方法：应用细胞外微电极录技术,记录麻醉大鼠海马齿状回颗粒细胞群体峰电位（PS）。结果：Rg1(10,100nmol/L)提高麻醉大鼠的基础突触传递,诱导海马齿状回突触传递长时程增强（LTP）,并提高高频刺激所诱导的LTP。选择性NOS抑制剂7－硝基吲唑（7－NI,5nmol)侧脑室注射可明显抑制Rg1所诱导的齿状回LTP,对基础突触传递无明显影响。L－Arg(250mg/kg,ip)可拮抗 7－NI对Rg1诱导LTP的抑制作用（P＜0．05）。结论：Rg1显著促进麻醉大鼠的突触传递效能,由神经元型NOS（nNOS）所产生的NO参与了Rg1对齿状回LTP的诱导过程。     

The induction of long-term potentiation at amygdalo-hippocampal synapses in vivo

Electrical stimulation of the basolateral amygdala (BLA) evoked synaptic potentials in the dentate gyrus (DG) of the hippocampus in anesthetized rats. To determine if this pathway possesses synaptic plasticity, we investigated the impact of several conditions of high-frequency stimulation on BLA-DG synaptic potentials in these rats. Application of two trains of 100-pulse, 100-Hz stimulation or theta-burst stimulation to the BLA reproducibly induced long-term potentiation (LTP) of BLA-DG synaptic potentials. Paired-pulse facilitation was unchanged during LTP, suggesting that postsynaptic mechanisms are involved in the expression of LTP. In addition, the induction of LTP was not affected by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate, suggesting that activation of NMDA receptors is not required. This novel form of LTP should be a valuable model for elucidating neural mechanisms underlying the formation of emotional memory.     

Effect of ginsenoside Rb1 on long-term potentiation in the dentate gyrus of anaesthetized rats

Ginsenosides are the major principles of Panax ginseng and have various pharmacological actions on the central nervous system. In this report, we investigated whether ginsenoside Rb1 (10, 100 nmol l^-1, icv) could increase the population spike (PS) amplitude in a dose-dependent manner, and accelerate the maintenance phase of long-term potentiation (LTP) induced by high frequency stimulation (HFS) in the dentate gyrus of anaesthetized rats. However, it had no effect on basic synaptic responses evoked by test stimulation. Comparatively, ginsenoside Rb1 (10, 100 nmol l^-1, icv) inhibited the induction phase of LTP induced by HFS in a dose-dependent manner. This may be one of the mechanisms of action of ginsenoside Rb1 on synaptic transmission. The details of the mechanism need further investigation.     

(-),(+)黄皮酰胺对大鼠海马突触传递功能的不同影响

采用细胞外电生理记录法记录了低频刺激所诱发的麻醉大鼠海马齿状回颗粒细胞层群峰电位(PS)并比较了侧脑室注射(-),(+)黄皮酰胺对PS及强直刺激所诱导的长时程增强效应(LTP)作用。结果表明:低剂量(1nmol)时,(-)或(+)黄皮酰胺都对基础状态下的PS没有影响。对LTP(+)黄皮酰胺也无作用,(-)黄皮酰胺表现为增强作用;将剂量提高至4nmol时,(-)黄皮酰胺对基础PS和LTP都有增强作用且对LTP的作用表现出一定的剂量依赖性,(+)黄皮酰胺对PS仍无影响,对LTP有一定的抑制作用。提示黄皮酰胺对海马齿状回突触传递活动的作用具有光学选择性,这一结果有力地支持了(-)黄皮酰胺促智作用的行为学和神经生化学研究结果。     

An increased expression of the mGlu5 receptor protein following LTP induction at the perforant path-dentate gyrus synapse in freely moving rats

The involvement of metabotropic glutamate (mGlu) receptors in the induction of long-term potentiation (LTP) in vivo has been consistently documented. We have investigated whether LTP induction in the dentate gyrus of rats leads to changes in expression of mGlu2/3 or -5 receptor subtypes in the hippocampus. LTP was induced at the medial perforant path-dentate gyrus synapses, and mGlu receptor expression was examined by Western blot or in situ hybridization. An up-regulation of mGlu5 receptors was observed in the hippocampus both 24 and 48 h following LTP induction. This effect was restricted to the dentate gyrus and CA1 region, whereas no changes in mGlu5 receptor protein (but an increase in mRNA levels) were observed in the CA3 region. The increased expression of mGlu5 receptors was directly related to the induction of LTP, because it was not observed when tetanic stimulation was carried out in animals treated with the NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5). Western blot analysis also showed a reduced expression of mGlu2/3 receptors in the whole hippocampus 24 h after LTP induction, indicating that the increased expression of mGlu5 receptors was specific. These data suggest that an up-regulation of mGlu5 receptors is a component of the plastic changes that follow the induction of LTP at the perforant path-dentate gyrus synapse.     

黄皮酰胺对清醒自由活动大鼠齿状回突触传递的影响

目的：研究黄皮酰胺对自由活动大鼠海马齿状回突触传递功能的作用。方法：采用细胞外电生理记录技术。结果：一次性施加HFS能稳定诱导出LTP并维持达5 d;(-)黄皮酰胺(8 mg.kg^-1,ig)组PS于连续给药的d 3开始明显增高,至d 5基本达最高值,连续给药7 d后停药,停药后5 d内增高的PS不见明显降低,而测试阈值呈现相反的变化;同剂量的(+)黄皮酰胺对PS和测试阈值无明显影响。结论：(-)黄皮酰胺经口给药也能在大鼠海马组织中达到影响突触传递活动的水平,提示黄皮酰胺对清醒自由活动大鼠海马齿状回突触传递的影响有手性选择性。     

Role of the group III metabotropic glutamate receptor in LTP, depotentiation and LTD in dentate gyrus of freely moving rats

We investigated whether group III metabotropic glutamate (mGlu) receptors are critically involved in the expression of long-term potentiation (LTP), depotentiation, or long-term depression (LTD) in the dentate gyrus of freely moving rats. Male Wistar rats (7 8 weeks) underwent implantation of stimulating and recording electrodes in the medial perforant path and dentate gyrus granule cell layer, respectively. A cannula was permanently implanted into the ipsilateral cerebral ventricle to enable drug administration. Intracerebral injection of the group III mGlu receptor agonist, L(+)-2-amino-4-phosphonobutanoic acid (AP4), significantly inhibited LTP at a concentration which unaffects basal synaptic transmission. Depotentiation. short-term depression (STD) and LTDwere unaffected by the agonist. The antagonist. (R.S)-r-cyclopropyl-4-phosphonophenylglycine (CPPG), inhibited agonist effects. but had no independent effects on basal synaptic transmission. CPPG did not affect the profile of LTP, depotentiation or STD elicited by low frequency stimulation (LFS) at 0.5 or 3 Hz. but significantly impaired LTD expression (at I Hz) and STD elicited at 5 Hz.These findings suggest that activation of group III mGlu receptors is critically required for LTD. but not LTP or depotentiation in the dentate gyrus and provide evidence for the involvement of separate mechanisms underlying LTD and depotentiation.