Glutamate-triggered events inducing corticostriatal long-term depression
Glutamate-triggered events inducing corticostriatal long-term depression
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DOI：
10.1523/jneurosci.19-14-06102.1999
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发表时间：
1999-07-15
影响因子：
5.3
通讯作者：
Bernardi, G
中科院分区：
文献类型：
--
作者：
Calabresi, P;Centonze, D;Bernardi, G
皮质纹状体纤维的重复激活产生纹状体棘神经元记录的兴奋性突触电位的长期抑制（LTD）。这种形式的突触可塑性可能被认为是某些形式的运动学习和记忆的可能神经基础。在本研究中，从大鼠皮质纹状体切片制备物中进行细胞内记录以研究谷氨酸和纹状体LTD的其他关键因素的作用。在电流钳实验中，而不是在电压钳实验中，短暂的谷氨酸局部应用以及皮质纹状体纤维的高频刺激（HFS）诱导LTD。这种药理学LTD和HFS诱导的LTD是相互闭塞的，提示两种形式的突触可塑性共享共同的诱导机制;分别通过AMPA和t-ACPD单独激活非NMDA离子型谷氨酸受体（iGluRs）或代谢型谷氨酸受体（mGluRs）未能产生皮质纹状体突触传递的显著长期变化。相反，LTD是在同时应用AMPA和t-ACPD后获得的。此外，quisqualate（一种激活iGluRs和I组mGluRs的化合物）也能够诱导这种形式的药理学LTD。单独或在t-ACPD和多巴胺（DA）存在下记录的神经元的电去极化未能模拟谷氨酸受体激活诱导LTD的作用。然而，当在t-ACPD共同给药之前，电去极化能够诱导LTD，DA和低剂量的羟胺，一种在组织中产生一氧化氮（NO）的化合物。没有这些化合物单独产生LTD。谷氨酸诱导的LTD，以及HFS诱导的LTD，被阻断的L-舒必利，D2 DA受体拮抗剂，和7-硝基吲唑盐，一氧化氮合酶抑制剂。本研究表明，皮质纹状体LTD的诱导需要四个主要因素：（1）突触后神经元的膜去极化;（2）mGluRs的激活;（3）DA受体的激活;（4）纹状体中间神经元释放NO。
Repetitive activation of corticostriatal fibers produces longterm depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of synaptic plasticity might be considered the possible neural basis of some forms of motor learning and memory. In the present study, intracellular recordings were performed from rat corticostriatal slice preparations to study the role of glutamate and other critical factors underlying striatal LTD. In current-clamp, but not in voltage-clamp experiments, brief focal applications of glutamate, as well as high-frequency stimulation (HFS) of corticostriatal fibers, induced LTD. This pharmacological LTD and the HFS-induced LTD were mutually occlusive, suggesting that both forms of synaptic plasticity share common induction mechanisms; Isolated activation of either non-NMDA-ionotropic glutamate receptors (iGluRs) or metabotropic glutamate receptors (mGluRs), respectively by AMPA and t-ACPD failed to produce significant long-term changes of corticostriatal synaptic transmission. Conversely, LTD was obtained after the simultaneous application of AMPA plus t-ACPD. Moreover, also quisqualate, a compound that activates both iGluRs and group I mGluRs, was able to induce this form of pharmacological LTD. Electrical depolarization of the recorded neurons either alone or in the presence of t-ACPD and dopamine (DA) failed to mimic the effects of the activation of glutamate receptors in inducing LTD. However, electrical depolarization was able to induce LTD when preceded by coadministration of t-ACPD, DA, and a low dose of hydroxylamine, a compound generating nitric oxide (NO) in the tissue. None of these compounds alone produced LTD. Glutamate-induced LTD, as well as the HFS-induced LTD, was blocked by L-sulpiride, a D2 DA receptor antagonist, and by 7-nitroindazole monosodium salt, a NO synthase inhibitor. The present study indicates that four main factors are required to induce corticostriatal LTD: (1) membrane depolarization of the postsynaptic neuron; (2) activation of mGluRs; (3) activation of DA receptors; and (4) release of NO from striatal interneurons.