Mechanisms underlying the inhibition of long-term potentiation by preconditioning stimulation in the hippocampus in vitro
Mechanisms underlying the inhibition of long-term potentiation by preconditioning stimulation in the hippocampus in vitro
复制标题
DOI：
10.1016/s0306-4522(03)00440-8
复制
发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Anwyl, R
中科院分区：
文献类型：
--
作者：
Gisabella, B;Rowan, MJ;Anwyl, R
我们研究了一种形式的后可塑性，即抑制预处理刺激的高频刺激（HFS）诱导的长时程增强（LTP）在内侧穿通路的齿状回的机制。预处理刺激（弱50 Hz）被发现抑制随后的LTP诱导，如果应用10-20分钟，但不是2或45分钟，之前的HFS。低频预处理刺激不能阻断LTP的诱导。LTP的抑制不是由N-甲基-D-天冬氨酸受体（NMDAR）传递的减少引起的，因为预处理刺激并没有减少孤立的NMDAR介导的EPSP。I组和II组代谢型谷氨酸受体（mGluR）的激活参与抑制LTP的实验表明，其中抑制LTP的预处理刺激被阻止的存在下，I组或II组mGluR的拮抗剂在预处理刺激。此外，组I和组II mGluR激动剂直接抑制随后的LTP诱导。NMDAR参与预处理刺激的能力表明，NMDAR拮抗剂，以防止预处理刺激抑制LTP。预处理抑制LTP诱导的激酶抑制剂的使用涉及PKC和p38 MAP激酶的激活，但不涉及p42 MAP激酶或酪氨酸激酶。我们的结论是，预处理抑制LTP诱导是一个复杂的过程，涉及激活NMDAR，组I和组II mGluR，和细胞内级联激活PKC和p38 MAP激酶。(C)2003年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We have investigated the mechanisms underlying a form of metaplasticity, namely the inhibition by preconditioning stimulation of high frequency stimulation (HFS)-induced long-term potentiation (LTP) in the medial perforant path of the dentate gyrus. Preconditioning stimulation (weak 50 Hz) was found to inhibit subsequent LTP induction if applied 10-20 min, but not 2 or 45 min, prior to the HFS. Preconditioning stimulation in the form of low frequency stimulation did not block LTP induction. The inhibition of LTP was not caused by a reduction in N-methyl-D-aspartate receptor (NMDAR) transmission, as the preconditioning stimulation did not reduce isolated NMDAR-mediated EPSPs. The involvement of group I and group II metabotropic glutamate receptor (mGluR) activation in the inhibition of LTP was demonstrated by experiments in which the inhibition of LTP by the preconditioning stimulation was prevented by the presence of antagonists of group I or group II mGluR during the preconditioning stimulation. Moreover, group I and group II mGluR agonists directly inhibited subsequent LTP induction. The involvement of NMDAR in the preconditioning stimulation was shown by the ability of an NMDAR antagonist to prevent the inhibition of LTP by the preconditioning stimulation. The preconditioning inhibition of LTP induction was shown by the use of kinase inhibitors to involve activation of PKC and p38 MAP kinase, but not p42 MAP kinase or tyrosine kinase. We conclude that the preconditioning inhibition of LTP induction is a complex process which involves activation of NMDAR, group I and group II mGluR, and intracellular cascades activating PKC and p38 MAP kinase. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.