Serrano Alexandre, Haddjeri Nasser, Lacaille Jean-Claude, Robitaille Richard
Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada.
J Neurosci. 2006 May 17;26(20):5370-82. doi: 10.1523/JNEUROSCI.5255-05.2006.
Tetanus-induced heterosynaptic depression in the hippocampus is a key cellular mechanism in neural networks implicated in learning and memory. A growing body of evidence indicates that glial cells are important modulators of synaptic functions, but very little is known about their role in heterosynaptic plasticity. We examined the role of glial cells in heterosynaptic depression, knowing that tetanization and NMDA application caused depression of synaptic field responses (fEPSPs) and induced Ca2+ rise in glial cells. Here we report that chelating Ca2+ in a glial syncytium interfered with heterosynaptic depression and NMDA-induced fEPSP depression, suggesting that Ca2+ activation of glial cells is necessary for heterosynaptic depression. The NMDA-induced Ca2+ rise in glial cells was sensitive to tetrodotoxin and reduced by the GABAB antagonist CGP55845. Both heterosynaptic depression and simultaneous Ca2+ activation of glial cells were prevented by CGP55845, suggesting an involvement of the GABAergic network in glial activation and heterosynaptic depression. Also, the GABAB agonist baclofen caused both a Ca2+ rise in glial cells and fEPSP depression. Heterosynaptic depression, as well as NMDA- and baclofen-induced depression, were attenuated by an A1 antagonist, cyclopentyl-theophylline, whereas glial cell activation was not, indicating a role of adenosine downstream of glial activation. Finally, heterosynaptic depression requires ATP degradation because ectonucleotidase inhibitors reduced this plasticity. Our work indicates that Ca2+ activation of glial cells is necessary for heterosynaptic depression, which involves the sequential interaction of Schaffer collaterals, the GABAergic network, and glia. Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses.
破伤风诱导的海马异突触抑制是神经网络中与学习和记忆相关的关键细胞机制。越来越多的证据表明，胶质细胞是突触功能的重要调节因子，但关于它们在异突触可塑性中的作用却知之甚少。我们研究了胶质细胞在异突触抑制中的作用，已知强直刺激和应用NMDA会导致突触场电位（fEPSP）抑制，并诱导胶质细胞内Ca2+升高。在此我们报告，在胶质细胞合体中螯合Ca2+会干扰异突触抑制和NMDA诱导的fEPSP抑制，这表明胶质细胞的Ca2+激活对于异突触抑制是必需的。NMDA诱导的胶质细胞内Ca2+升高对河豚毒素敏感，并被GABAB拮抗剂CGP55845降低。CGP55845可同时阻止异突触抑制和胶质细胞的Ca2+激活，这表明GABA能网络参与了胶质细胞激活和异突触抑制。此外，GABAB激动剂巴氯芬会导致胶质细胞内Ca2+升高和fEPSP抑制。异突触抑制以及NMDA和巴氯芬诱导的抑制，均被A1拮抗剂环戊基茶碱减弱，而胶质细胞激活则不受影响，这表明腺苷在胶质细胞激活的下游发挥作用。最后，异突触抑制需要ATP降解，因为外核苷酸酶抑制剂会降低这种可塑性。我们的研究表明，胶质细胞的Ca2+激活对于异突触抑制是必需的，而异突触抑制涉及谢弗侧支、GABA能网络和胶质细胞的顺序相互作用。因此，在哺乳动物中枢兴奋性突触的异突触可塑性形成过程中，胶质细胞和神经元网络在功能上相互关联。
