Department of Neurosurgery, University Clinic Bonn, Bonn, Germany.
Synapse. 2009 Dec;63(12):1060-8. doi: 10.1002/syn.20692.
Mossy fiber long-term depression (LTD) has been shown to be triggered by either pharmacological or synaptic activation of Group II metabotropic glutamate receptors (mGluRs) whereas other studies indicate that synaptic activation of mGluRs is very limited. Therefore, we reexamined the role of Group II mGluRs for the induction of mossy fiber LTD. The complete depression of field potentials (fEPSPs) by 1 microM (2S,2'R,3'R)-2-(2',3'-Dicarboxycyclopropyl)glycine (DCG-IV) only partially reversed upon removal of the drug but fEPSPs were completely restored by the Group II antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY341495) (3 microM). In contrast, fEPSPs returned back to baseline within 30 min after a brief application of 0.2 microM DCG-IV suggesting that the incomplete reversal of higher concentrations may be due to a residual receptor occupancy rather than to an induction of LTD. LY341495 itself did not increase fEPSPs and also blocked the inhibition of (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-I) (20 microM) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) (10 microM) and its effect was mimicked by CPPG (50 microM). Furthermore, stimulation at 1 Hz for 15 min induced an LTD of 81% +/- 3% and 80% +/- 4% in the absence and presence of LY341495, respectively (n = 7, 5). Finally, we found that synaptic activation of Group II mGluRs during 15 min of 1-Hz stimulation only produces an inhibition of release by 8% +/- 1% (30 degrees C, n = 3). Our data suggests that pharmacological activation of Group II mGluRs is fully reversible per se and does not produce a long lasting depression and that activation of Group II mGluRs is neither necessary nor sufficient for the induction of mossy fiber LTD.
苔藓纤维 LTD 已被证实可由药理学或 II 组代谢型谷氨酸受体（mGluR）的突触激活引发，而其他研究表明 mGluR 的突触激活非常有限。因此，我们重新检查了 II 组 mGluR 对苔藓纤维 LTD 诱导的作用。1 μM（2S,2'R,3'R）-2-（2',3'-二羧基环丙基）甘氨酸（DCG-IV）对场电位（fEPSP）的完全抑制，在药物去除后仅部分反转，但 fEPSP 被 II 组拮抗剂 2S-2-氨基-2-（1S,2S-2-羧基环丙基-1-基）-3-（黄嘌呤-9-基）丙酸（LY341495）（3 μM）完全恢复。相比之下，在应用 0.2 μM DCG-IV 后 30 分钟内，fEPSP 恢复到基线内，这表明较高浓度不完全反转可能是由于残留受体占有率而不是 LTD 的诱导。LY341495 本身不会增加 fEPSP，也会阻断（2S,1'S,2'S）-2-（2-羧基环丙基）甘氨酸（L-CCG-I）（20 μM）和（1S,3R）-1-氨基环戊烷-1,3-二羧酸（ACPD）（10 μM）的抑制作用，其作用被 CPPG（50 μM）模拟。此外，在无 LY341495 和存在 LY341495 的情况下，1 Hz 刺激 15 分钟分别诱导 81% +/- 3%和 80% +/- 4%的 LTD（n = 7,5）。最后，我们发现，在 1-Hz 刺激 15 分钟期间，II 组 mGluR 的突触激活仅导致释放抑制 8% +/- 1%（30°C，n = 3）。我们的数据表明，药理学激活 II 组 mGluR 本身是完全可逆的，不会产生持久的抑制，并且激活 II 组 mGluR 对于诱导苔藓纤维 LTD 既不是必需的也不是充分的。
