DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists
DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists
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DOI：
10.1016/s0028-3908(99)00123-9
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发表时间：
1999-10-01
影响因子：
4.7
通讯作者：
Collingridge, GL
中科院分区：
文献类型：
--
作者：
Fitzjohn, SM;Kingston, AE;Collingridge, GL
我们用细胞外微电极记录了一种突触传递的长时程抑制（LTD）形式，它可以由代谢型谷氨酸（mGlu）受体激活引起的年轻（12-18天）大鼠海马CAI区。特异性激动剂3，5-二羟基苯甘氨酸（DHPG）激活I组mGlu受体可诱导场兴奋性突触后电位（fEPSP）的LTD。mGlu，选择性激动剂2-氯-5-羟基苯甘氨酸也能够诱导LTD。相反，第II组特异性激动剂DCG-IV对突触传递没有影响，而第III组受体激动剂（S）-2-氨基-4-膦酰基丁酸酯引起抑郁，在激动剂洗脱后完全逆转。DHPG诱导的LTD仍然可以产生之前的电诱导的NMDA受体依赖的LTD的饱和后。DHPG诱导的LTD被逆转的强直刺激，包括100次电击，在100 Hz。新型mGlu受体拮抗剂（RS）-2-氨基-2-（3-顺式和反式-羧基环丁基-3-（9-噻吨基）丙酸）与其他mGlu受体拮抗剂一样，LY 393053也逆转了预先建立的DHPG诱导的LTD。相反，有效的mGlu，选择性拮抗剂（S）-2-甲基-4-羧基苯甘氨酸（LY 367385）不能阻止DHPG诱导的LTD的诱导。总之，DHPG可能通过激活mGlu（5）受体，能够在年轻大鼠海马CA 1区诱导一种强有力的LTD形式，这种LTD与NMDA受体依赖的同源突触LTD在机制上不同。C）1999 Elsevier Science Ltd.保留所有权利。
We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CAI region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu, selective agonist 2-chloro-5 -hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu, and mGlu, receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu, selective antagonist (S)-2methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu(5) receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD. (C) 1999 Elsevier Science Ltd. All rights reserved.