Naie Katja, Tsanov Marian, Manahan-Vaughan Denise
Institute for Physiology of the Charité, Synaptic Plasticity Research Group, Humboldt University, Berlin, Germany.
Eur J Neurosci. 2007 Jun;25(11):3264-75. doi: 10.1111/j.1460-9568.2007.05583.x.
The existence of long-term depression (LTD) in the dentate gyrus of freely moving rats, as well as the contribution of different types of metabotropic glutamate receptors (mGluRs) to this form of plasticity, has been the subject of much debate. Here, we describe two distinct forms of mGluR-dependent hippocampal LTD in the dentate gyrus of freely moving adult rats. LTD, induced by low-frequency stimulation (LFS) of the medial perforant path (LFS-LTD), was prevented by antagonism of the phospholipase C-coupled receptors, mGluR1 but not mGluR5. Chemical LTD, induced by intracerebral application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine, was blocked by antagonism of both mGluR5 and mGluR1. Selective activation of mGluR5, using (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), also led to chemical LTD. To test whether LFS-LTD and chemical LTD share common induction mechanisms, we applied LFS following the induction of chemical LTD by CHPG (CHPG-LTD). Surprisingly, LFS impaired CHPG-LTD. Further analysis revealed that induction of CHPG-LTD led to altered calcium dynamics sufficient for its reversal by LFS. We found that LTD induced by (R,S)-3,5-dihydroxyphenylglycine, but not by CHPG, is impaired by N-methyl-d-aspartate receptor antagonism. Both forms of chemical LTD strongly require calcium influx through L-type voltage-gated calcium channels. This contrasts with previous findings that LFS-LTD in the dentate gyrus is both N-methyl-d-aspartate receptor and voltage-gated calcium channel independent. LFS-LTD and LTD induced by group I mGluR agonists thus appear to comprise distinct forms of LTD that require the activation of specific group I mGluRs and recruit calcium from different sources.
自由活动大鼠齿状回中长时程抑制（LTD）的存在，以及不同类型的代谢型谷氨酸受体（mGluRs）对这种可塑性形式的作用，一直是众多争论的主题。在此，我们描述了自由活动成年大鼠齿状回中两种不同形式的依赖于mGluR的海马LTD。由内侧穿通通路的低频刺激（LFS）诱导的LTD（LFS-LTD），可被磷脂酶C偶联受体mGluR1而非mGluR5的拮抗剂所阻断。由脑内应用I组mGluR激动剂（R,S）-3,5-二羟基苯甘氨酸诱导的化学性LTD，可被mGluR5和mGluR1的拮抗剂所阻断。使用（R,S）-2-氯-5-羟基苯甘氨酸（CHPG）选择性激活mGluR5，也会导致化学性LTD。为了测试LFS-LTD和化学性LTD是否共享共同的诱导机制，我们在CHPG诱导化学性LTD（CHPG-LTD）后施加LFS。令人惊讶的是，LFS损害了CHPG-LTD。进一步分析表明，CHPG-LTD的诱导导致钙动力学改变，足以使其被LFS逆转。我们发现，由（R,S）-3,5-二羟基苯甘氨酸而非CHPG诱导的LTD，会被N-甲基-D-天冬氨酸受体拮抗剂所损害。两种形式的化学性LTD都强烈需要通过L型电压门控钙通道的钙内流。这与之前的发现形成对比，即齿状回中的LFS-LTD既不依赖N-甲基-D-天冬氨酸受体也不依赖电压门控钙通道。因此，LFS-LTD和由I组mGluR激动剂诱导的LTD似乎包含不同形式的LTD，它们需要特定I组mGluRs的激活，并从不同来源募集钙。
