The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus
The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus
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DOI：
10.1016/s0028-3908(97)00181-0
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发表时间：
1997-11-01
影响因子：
4.7
通讯作者：
Collingridge, GL
中科院分区：
文献类型：
--
作者：
Palmer, MJ;Irving, AJ;Collingridge, GL
用脂隙记录技术测定了I组特异性代谢性谷氨酸(MGlu)受体激动剂(RS)-3，5-二羟基苯甘氨酸(DHPG)(100mU，10min)对成年大鼠海马脑片CA1区突触传递的长时程抑制(LTD)。在“正常”(含1 mM镁离子)介质中，LTD(在DHPG清洗30min后测量)很小(13+/-3%)，但当组织变得过度兴奋时，如果施加DHPG，则LTD增强，无论是通过从灌流液中去掉镁(35+/-3%)或添加GABA(A)受体拮抗剂印防己毒素(29+/-2%)。N-甲基-D-天冬氨酸(NMDA)受体拮抗剂AP5(100mM)可显著减少无镁条件下DHPG诱导的LTD的生成，但对印防己毒素诱导的LTD无明显影响。在无镁介质中，诱导LTD所需的DHPG阈值浓度为1~3 mU M，既不是II组(100 nM DCG-IV或1 mU M LY354740)或III组(10 mU M L-AP4)mGlu受体的特异性激动剂，也不是I组和II组联合激动剂(30~100 mU M(1S，3R)-AcPD)诱导的LTD。然而，激活mGlu(5)而不激活mGlu(1)受体的激动剂(1 MM CHPG)确实能诱导LTD。令人惊讶的是，DHPG诱导的LTD可被mGlu受体拮抗剂逆转，MGlu受体拮抗剂在DHPG被清除数小时后应用。在无镁介质中，DHPG诱导的LTD与突触激活(1200个刺激，频率2赫兹)引起的LTD不阻断。这些数据表明，激活I组mGlu受体(可能是mGlu(5))可以诱导LTD，这种mGlu受体介导的LTD可能需要也可能不需要激活NMDA受体，这取决于实验条件。(C)1998爱思唯尔科学有限公司。保留所有权利。
The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) (100 mu M, 10 min) induced long term depression (LTD) of synaptic transmission in the CA1 region of adult rat hippocampal slices, measured using a grease-gap recording technique. In "normal" (1 mM Mg2+-containing) medium, LTD (measured 30 min after washout of DHPG) was small(13 +/- 3 %), but LTD was enhanced if DHPG was applied when the tissue was made hyperexcitable, either by omitting Mg2+ from the perfusate (35 +/- 3 %) or by adding the GABA(A) receptor antagonist picrotoxin (29 +/- 2 %). The N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (100 mu M) substantially reduced the generation of DHPG-induced LTD in Mg2+-free medium, but had little effect on LTD induced in the presence of picrotoxin. In Mg2+-free medium, the threshold concentration of DHPG required to induce LTD was between 1 and 3 mu M. Neither agonists specific for group II (100 nM DCG-IV or 1 mu M LY354740) or group III (10 mu M L-AP4) mGlu receptors or a combined group I and II agonist (30-100 mu M (1S,3R)-ACPD) induced LTD. However, an agonist (1 mM CHPG) which activates mGlu(5) but not mGlu(1) receptors did induce LTD. Surprisingly, DHPG-induced LTD was reversed by mGlu receptor antagonists, applied hours after washout of DHPG. DHPG-induced LTD did not occlude with LTD induced by synaptic activation (1200 stimuli delivered at 2 Hz), in Mg2+-free medium. These data show that activation of group I mGlu receptors (probably mGlu(5)) can induce LTD and that this mGlu receptor-mediated LTD may, or may not, require activation of NMDA receptors, depending on the experimental conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.