NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus
NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus
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DOI：
10.1111/j.1476-5381.1996.tb16028.x
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发表时间：
1996-11-01
影响因子：
7.3
通讯作者：
Collingridge, GL
中科院分区：
文献类型：
--
作者：
Harvey, J;Palmer, MJ;Collingridge, GL
1采用脂隙法和细胞内记录技术，研究了特异性代谢型谷氨酸受体（mGlu）激动剂(1S,3R)-1-氨基环戊烷-1,3-二羧酸（(1S,3R)-ACPD）对4-10周龄大鼠海马CA1区突触传递的抑制作用在1mm Mg2+存在下，(1S,3R)-ACPD是一种弱突触抑制剂。相反，在不添加Mg2+的情况下，(1S,3R)-ACPD在抑制α -氨基-3-羟基-5-甲基异唑-4-丙酸（AMPA）和n -甲基- d -天冬氨酸（NMDA）受体介导的突触传递组分方面更有效。在100 μ M时，(1S,3R)- acpd使持有的兴奋性突触后电位（e.p.s.p）斜率降低了96 +/- 1%（平均值+/- s.e.平均值，n = 7），而在1 mM含Mg2+的培养基中（n = 17），其斜率为23 +/- 4%特异性NMDA受体拮抗剂(R)-2-氨基-5-磷酸戊酸酯（AP5; 100 μ M）使100 μ M (1S,3R)- acpd在无Mg2+培养基中的抑制作用从96 +/- 1降低到46 +/- 6% （n = 7）微毒素（50 μ M）和CGP 55845A （1 μ M）在1 mM Mg2+存在下阻断GABA受体介导的突触传递的两个组分也使(1S,3R)- acpd （100 μ M）的抑制作用从29 +/- 5%提高到67 +/- 6% (n = 6) 5在无Mg2+的培养基中，(1S,3R)-ACPD的作用被mGlu拮抗剂(+)- α -甲基-4-羧基苯基甘氨酸（(+)-MCPG）拮抗。因此，30 μ M (1S,3R)- acpd诱导的下降由1 mM (+)- mcpg .6从48 +/- 4%逆转到8 +/- 6% （n = 4）在无Mg2+的培养基中，1组mGlu激动剂(RS)-3,5-二羟基苯基甘氨酸（DHPG; 100 μ M）使突触反应降低74 +/- 2% （n = 18）。II组激动剂((2S,1'S,2' s)-2-（2'-羧基环丙基）甘氨酸；L-CCG-1;10 μ M；n = 4)和(2S, 1'R,2' r,3' r)-2-（2',3'-二羧基环丙基）甘氨酸；DCG-IV;100海里;n = 3)和III组激动剂((S)-2-氨基-4-磷酸丁酸；L-AP4;10 μ M；N = 4)有任何影响在细胞内记录的(1S,3R)-ACPD的去极化作用在Mg2+存在和不存在的情况下是相似的。在无Mg2+的介质中，AP5对(1S,3R)- acpd诱导的去极化没有影响。因此，50 μ M (1S,3R)- acpd分别在3种条件下诱导了9 +/- 3mv （n = 5）、10 +/- 2mv （n = 4）和8 +/- 2mv （n = 5）的去极化当50 μ M (1S,3R)- acpd存在时，将膜电位恢复到初始水平，1 mM Mg2+ (n = 5)使e.p.s.p.振幅增强8 +/- 3%，而没有Mg2+ (n = 4)时，e.p.s.p.振幅下降37 +/- 11%。9 .添加AP5可抑制(1S,3R)- acpd诱导的epsp下降（4 +/- 5% (n = 5)）由此可见，1组glu激动剂的激活以NMDA受体依赖的方式导致兴奋性突触传递的抑制。
1 The depression of synaptic transmission by the specific metabotropic glutamate receptor (mGlu) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) was investigated in area CA1 of the hippocampus of 4-10 week old rats, by use of grease-gap and intracellular recording techniques.2 In the presence of 1 mM Mg2+, (1S,3R)-ACPD was a weak synaptic depressant. In contrast, in the absence of added Mg2+, (1S,3R)-ACPD was much more effective in depressing both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of synaptic transmission. At 100 mu M, (1S,3R)-ACPD depressed the slope of the held excitatory postsynaptic potential (e.p.s.p.) by 96 +/- 1% (mean +/- s.e. mean; n = 7) compared with 23 +/- 4% in 1 mM Mg2+-containing medium (n = 17).3 The depressant action of 100 mu M (1S,3R)-ACPD in Mg2+-free medium was reduced from 96 +/- 1 to 46 +/- 6% (n = 7) by the specific NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 100 mu M).4 Blocking both components of GABA receptor-mediated synaptic transmission with picrotoxin (50 mu M) and CGP 55845A (1 mu M) in the presence of 1 mM Mg2+ also enhanced the depressant action of (1S,3R)-ACPD (100 mu M) from 29 +/- 5 to 67 +/- 6% (n = 6).5 The actions of (1S,3R)-ACPD, recorded in Mg2+-free medium, were antagonized by the mGlu antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). Thus, depressions induced by 30 mu M (1S,3R)-ACPD were reversed from 48 +/- 4 to 8 +/- 6% (n = 4) by 1 mM (+)-MCPG.6 In Mg2+-free medium, a group I mGlu agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 mu M) depressed synaptic responses by 74 +/- 2% (n = 18). In contrast, neither the group II agonists ((2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine; L-CCG-1; 10 mu M; n = 4) and ((2S, 1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine; DCG-IV; 100 nM; n = 3) nor the group III agonist ((S)-2-amino-4-phosphonobutanoic acid; L-AP4; 10 mu M; n = 4) had any effect.7 The depolarizing action of (1S,3R)-ACPD, recorded intracellularly, was similar in the presence and absence of Mg2+. AP5 did not affect the (1S,3R)-ACPD-induced depolarization in Mg2+-free medium. Thus, 50 mu M (1S,3R)-ACPD induced depolarizations of 9 +/- 3 mV (n = 5), 10 +/- 2 mV (n = 4) and 8 +/- 2 mV (n = 5) in the three respective conditions.8 On resetting the membrane potential in the presence of 50 mu M (1S,3R)-ACPD to its initial level, the e.p.s.p. amplitude was enhanced by 8 +/- 3% in 1 mM Mg2+ (n = 5) compared with a depression of 37 +/- 11% in the absence of Mg2+ (n = 4). Addition of AP5 prevented the (1S,3R)-ACPD-induced depression of the e.p.s.p. (depression of 4 +/- 5% (n = 5)).9 It is concluded that activation by group 1 mGlu agonists results in a depression of excitatory synaptic transmission in an NMDA receptor-dependent manner.