Nicoll R A, Oliet S H, Malenka R C
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
Neurobiol Learn Mem. 1998 Jul-Sep;70(1-2):62-72. doi: 10.1006/nlme.1998.3838.
We have found that two distinct forms of long-term depression (LTD), one dependent on the activation of NMDA receptors (NMDARs) and the other dependent on the activation of metabotropic glutamate receptors (mGluRs), coexist in pyramidal cells of the CA1 region of the hippocampus of juvenile rats (11-35 days). Both forms were pathway specific, required membrane depolarization, and were blocked by chelating postsynaptic Ca2+ with BAPTA. The mGluR-LTD, but not the NMDAR-LTD, was blocked by the T-type Ca2+ channel blocker Ni2+ and intracellular administration of a protein kinase C inhibitory peptide. In contrast, the protein phosphatase inhibitor Microcystin LR blocked NMDAR-LTD, but not mGluR-LTD. NMDAR-LTD is associated with a decrease in the size of quantal excitatory postsynaptic currents, whereas for mGluR-LTD there was no change in quantal size, but a large decrease in the frequency of events. While mGluR-LTD did not interact with NMDAR-dependent long term potentiation (LTP), NMDAR-LTD was capable of reversing LTP. Prior saturation of mGluR-LTD had no effect on NMDAR-LTD. NMDAR-LTD and mGluR-LTD thus appear to be mechanistically distinct forms of synaptic plasticity in that they share neither induction nor expression mechanisms.
我们发现，两种不同形式的长时程抑制（LTD），一种依赖于N-甲基-D-天冬氨酸受体（NMDARs）的激活，另一种依赖于代谢型谷氨酸受体（mGluRs）的激活，共存于幼年大鼠（11 - 35天）海马CA1区锥体细胞中。两种形式均具有通路特异性，需要膜去极化，并且通过用1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）螯合突触后Ca2+来阻断。代谢型谷氨酸受体依赖性长时程抑制（mGluR-LTD），而非N-甲基-D-天冬氨酸受体依赖性长时程抑制（NMDAR-LTD），可被T型Ca2+通道阻滞剂镍离子（Ni2+）和细胞内给予蛋白激酶C抑制肽所阻断。相反，蛋白磷酸酶抑制剂微囊藻毒素LR可阻断NMDAR-LTD，而不阻断mGluR-LTD。NMDAR-LTD与量子兴奋性突触后电流大小的降低有关，而对于mGluR-LTD，量子大小没有变化，但事件频率大幅降低。虽然mGluR-LTD不与NMDAR依赖性长时程增强（LTP）相互作用，但NMDAR-LTD能够逆转LTP。mGluR-LTD的预先饱和对NMDAR-LTD没有影响。因此，NMDAR-LTD和mGluR-LTD似乎是机制上不同的突触可塑性形式，因为它们既不共享诱导机制也不共享表达机制。
