Inserm, Unité 862, Neurocentre Magendie, 33077 Bordeaux, France.
J Neurosci. 2012 Jan 25;32(4):1301-10. doi: 10.1523/JNEUROSCI.3017-11.2012.
Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter release. We here report that applications of agonists of GluK1-containing KARs in the rat supraoptic nucleus has an opposite action on glutamatergic transmission according to the phenotype of the postsynaptic neuron. Whereas glutamate release was facilitated in oxytocin (OT) neurons, it was inhibited in vasopressin (VP) cells. Interestingly, an antagonist of GluK1-containing KARs caused an inhibition of glutamate release in both OT and VP neurons, revealing the existence of tonically activated presynaptic KARs that are positively coupled to transmitter release. We thus postulated that the inhibition of glutamate release observed with exogenous applications of GluK1 agonists on VP neurons could be indirect. In agreement with this hypothesis, we first showed that functional GluK1-containing KARs were present postsynaptically on VP neurons but not on OT cells. We next showed that the inhibitory effect induced by exogenous GluK1 receptor agonist was compromised when BAPTA was added in the recording pipette to buffer intracellular Ca2+ and block the release of a putative retrograde messenger. Under these conditions, GluK1-containing KAR agonist facilitates glutamatergic transmission in VP neurons in a manner similar to that observed for OT neurons and that resulted from the activation of presynaptic GluK1 receptors. GluK1-mediated inhibition of glutamate release in VP neurons was also blocked by a κ-opioid receptor antagonist. These findings suggest that activation of postsynaptic GluK1-containing KARs on VP neurons leads to the release of dynorphin, which in turn acts on presynaptic κ-opioid receptors to inhibit glutamate release.
突触前 kainate 受体 (KAR) 对递质释放发挥调节作用。我们在此报告，在大鼠视上核中应用包含 GluK1 的 KAR 激动剂会根据突触后神经元的表型对谷氨酸能传递产生相反的作用。虽然谷氨酸释放在催产素 (OT) 神经元中被促进，但在加压素 (VP) 细胞中被抑制。有趣的是，包含 GluK1 的 KAR 拮抗剂在 OT 和 VP 神经元中均引起谷氨酸释放抑制，表明存在被紧张激活的突触前 KAR，它们与递质释放呈正偶联。因此，我们假设在外源性应用包含 GluK1 的激动剂时观察到的 VP 神经元中谷氨酸释放的抑制可能是间接的。与这一假说一致，我们首先表明，功能性包含 GluK1 的 KAR 存在于 VP 神经元的突触后，但不存在于 OT 细胞中。我们接下来表明，当在记录电极中添加 BAPTA 以缓冲细胞内 Ca2+并阻止假定的逆行信使释放时，外源性 GluK1 受体激动剂诱导的抑制作用会受到损害。在这些条件下，包含 GluK1 的 KAR 激动剂以类似于 OT 神经元的方式促进 VP 神经元中的谷氨酸能传递，并且源自突触前 GluK1 受体的激活。GluK1 介导的 VP 神经元中谷氨酸释放的抑制也被 κ-阿片受体拮抗剂阻断。这些发现表明，激活 VP 神经元上的突触后包含 GluK1 的 KAR 导致强啡肽的释放，反过来，强啡肽作用于突触前 κ-阿片受体以抑制谷氨酸释放。
