Inserm U 862, Neurocentre Magendie, 33077 Bordeaux France.
J Neurosci. 2010 Jan 20;30(3):985-95. doi: 10.1523/JNEUROSCI.3389-09.2010.
Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter release. This effect can be switched from facilitation to inhibition by an increased concentration of KAR agonists. We here report that activation of presynaptic GluK1-containing KARs facilitates GABA release on oxytocin and vasopressin neurons in the supraoptic nucleus of the hypothalamus. Increase in ambient levels of glutamate associated with the physiological reduction of astrocytic coverage of oxytocin neurons in lactating rats switches this KAR-mediated facilitation to inhibition of GABAergic transmission. This effect was reproduced in both oxytocin and vasopressin neurons of virgin rats when glutamate transporters were blocked pharmacologically, thereby establishing that enhanced levels of extracellular glutamate induce the switch in KAR-mediated action. The facilitation of GABA release was inhibited with philanthotoxin, a Ca(2+)-permeable KAR antagonist, suggesting that this effect was associated with an ionotropic mode of action. Conversely, KAR-mediated inhibition was compromised in the presence of U73122, a phospholipase C inhibitor, in agreement with the involvement of a metabotropic pathway. We thus reveal that physiological astrocytic plasticity modifies the mode of action of presynaptic KARs, thereby inversing their coupling with GABA release.
突触前 kainate 受体 (KARs) 对递质释放发挥调节作用。这种效应可以通过增加 KAR 激动剂的浓度从易化作用转变为抑制作用。我们在这里报告，激活包含 GluK1 的突触前 KARs 可促进下丘脑视上核中催产素和加压素神经元的 GABA 释放。与哺乳期大鼠中星形胶质细胞对催产素神经元覆盖减少相关的谷氨酸环境水平升高，将这种 KAR 介导的易化作用转变为 GABA 能传递的抑制作用。当谷氨酸转运体被药理学阻断时，这种效应在处女大鼠的催产素和加压素神经元中得到重现，从而证明细胞外谷氨酸水平的升高诱导了 KAR 介导作用的转变。用亲环素，一种 Ca(2+) 通透性 KAR 拮抗剂，抑制 GABA 释放的易化作用，表明这种作用与离子型作用模式有关。相反，在存在磷脂酶 C 抑制剂 U73122 的情况下，KAR 介导的抑制作用受损，这与代谢型途径的参与一致。因此，我们揭示了生理星形胶质细胞可塑性改变了突触前 KAR 的作用模式，从而逆转了它们与 GABA 释放的偶联。
