Department of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Department of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Cell Rep. 2023 Jul 25;42(7):112775. doi: 10.1016/j.celrep.2023.112775. Epub 2023 Jul 11.
Ionotropic glutamate receptors (GluRs) are targets for modulation in Hebbian and homeostatic synaptic plasticity and are remodeled by development, experience, and disease. We have probed the impact of synaptic glutamate levels on the two postsynaptic GluR subtypes at the Drosophila neuromuscular junction, GluRA and GluRB. We first demonstrate that GluRA and GluRB compete to establish postsynaptic receptive fields, and that proper GluR abundance and composition can be orchestrated in the absence of any synaptic glutamate release. However, excess glutamate adaptively tunes postsynaptic GluR abundance, echoing GluR scaling observed in mammalian systems. Furthermore, when GluRA vs. GluRB competition is eliminated, GluRB becomes insensitive to glutamate modulation. In contrast, GluRA is now homeostatically regulated by excess glutamate to maintain stable miniature activity, where Ca permeability through GluRA receptors is required. Thus, excess glutamate, GluR competition, and Ca signaling collaborate to selectively target GluR subtypes for homeostatic regulation at postsynaptic compartments.
离子型谷氨酸受体（GluRs）是赫布和动态平衡突触可塑性的调节靶点，并且由发育、经验和疾病进行重塑。我们探究了突触谷氨酸水平对果蝇肌神经接点的两种突触后 GluR 亚型（GluRA 和 GluRB）的影响。我们首先证明了 GluRA 和 GluRB 竞争建立突触后感受野，并且在没有任何突触谷氨酸释放的情况下，可以协调适当的 GluR 丰度和组成。然而，过量的谷氨酸适应性地调节突触后 GluR 的丰度，反映了在哺乳动物系统中观察到的 GluR 比例变化。此外，当 GluRA 与 GluRB 竞争消除时，GluRB 对谷氨酸调节变得不敏感。相比之下，GluRA 现在通过过量谷氨酸进行自身稳态调节以维持稳定的微小活动，需要通过 GluRA 受体的 Ca 通透性。因此，过量谷氨酸、GluR 竞争和 Ca 信号协同作用，选择性地针对突触后隔室的 GluR 亚型进行自身稳态调节。
