Maejima T, Hashimoto K, Yoshida T, Aiba A, Kano M
Department of Physiology, Kanazawa University School of Medicine, Takara-machi, Kanazawa 920-8640, Japan.
Neuron. 2001 Aug 16;31(3):463-75. doi: 10.1016/s0896-6273(01)00375-0.
We report a type of synaptic modulation that involves retrograde signaling from postsynaptic metabotropic glutamate receptors (mGluRs) to presynaptic cannabinoid receptors. Activation of mGluR subtype 1 (mGluR1) expressed in cerebellar Purkinje cells (PCs) reduced neurotransmitter release from excitatory climbing fibers. This required activation of G proteins but not Ca2+ elevation in postsynaptic PCs. This effect was occluded by a cannabinoid agonist and totally abolished by cannabinoid antagonists. Depolarization-induced Ca2+ transients in PCs also caused cannabinoid receptor-mediated presynaptic inhibition. Thus, endocannabinoid production in PCs can be initiated by two distinct stimuli. Activation of mGluR1 by repetitive stimulation of parallel fibers, the other excitatory input to PCs, caused transient cannabinoid receptor-mediated depression of climbing fiber input. Our data highlight a signaling mechanism whereby activation of postsynaptic mGluR retrogradely influences presynaptic functions via endocannabinoid system.
我们报告了一种突触调制类型，其涉及从突触后代谢型谷氨酸受体（mGluRs）到突触前大麻素受体的逆行信号传导。在小脑浦肯野细胞（PCs）中表达的mGluR亚型1（mGluR1）的激活减少了兴奋性攀缘纤维的神经递质释放。这需要G蛋白的激活，但不需要突触后PCs中的Ca2+升高。这种效应被大麻素激动剂阻断，并被大麻素拮抗剂完全消除。PCs中去极化诱导的Ca2+瞬变也导致大麻素受体介导的突触前抑制。因此，PCs中的内源性大麻素产生可以由两种不同的刺激引发。通过重复刺激平行纤维（PCs的另一种兴奋性输入）激活mGluR1，会导致短暂的大麻素受体介导的攀缘纤维输入抑制。我们的数据突出了一种信号传导机制，即突触后mGluR的激活通过内源性大麻素系统逆行影响突触前功能。
