Min M Y, Rusakov D A, Kullmann D M
Department of Clinical Neurology, Institute of Neurology, London, United Kingdom.
Neuron. 1998 Sep;21(3):561-70. doi: 10.1016/s0896-6273(00)80566-8.
Glutamatergic transmission at mossy fiber (MF) synapses on CA3 pyramidal neurons in the hippocampus is mediated by AMPA, kainate, and NMDA receptors and undergoes presynaptic modulation by metabotropic glutamate receptors. The recruitment of different receptors has thus far been studied by altering presynaptic stimulation to modulate glutamate release and interfering pharmacologically with receptors and transporters. Here, we introduce two novel experimental manipulations that alter the fate of glutamate molecules following release. First, an enzymatic glutamate scavenger reduces the postsynaptic response as well as presynaptic modulation by metabotropic receptors. At physiological temperature, however, the scavenger is effective only when glutamate uptake is blocked, revealing a role of active transport in both synaptic and extrasynaptic communication. Second, AMPA and kainate receptor-mediated postsynaptic signals are enhanced when extracellular diffusion is retarded by adding dextran to the perfusion solution, as is feedback modulation by metabotropic receptors, suggesting that the receptors are not saturated under baseline conditions. These results show that manipulating the spatiotemporal profile of glutamate following exocytosis can alter the involvement of different receptors in synaptic transmission.
海马体中CA3锥体神经元苔藓纤维（MF）突触处的谷氨酸能传递由AMPA、海人酸和NMDA受体介导，并受到代谢型谷氨酸受体的突触前调制。迄今为止，通过改变突触前刺激以调节谷氨酸释放以及通过药理学方法干扰受体和转运体来研究不同受体的募集情况。在此，我们介绍两种新颖的实验操作，它们可改变谷氨酸分子释放后的命运。首先，一种酶促谷氨酸清除剂可降低突触后反应以及代谢型受体的突触前调制。然而，在生理温度下，只有当谷氨酸摄取被阻断时，清除剂才有效，这揭示了主动转运在突触和突触外通讯中的作用。其次，当向灌注溶液中添加葡聚糖以阻碍细胞外扩散时，AMPA和海人酸受体介导的突触后信号会增强，代谢型受体的反馈调制也是如此，这表明在基线条件下受体并未饱和。这些结果表明，操纵胞吐作用后谷氨酸的时空分布可改变不同受体在突触传递中的参与情况。
