Ohno-Shosaku T, Maejima T, Kano M
Department of Physiology, Kanazawa University School of Medicine, 920-8640, Kanazawa, Japan.
Neuron. 2001 Mar;29(3):729-38. doi: 10.1016/s0896-6273(01)00247-1.
Endogenous cannabinoids are considered to function as diffusible and short-lived modulators that may transmit signals retrogradely from postsynaptic to presynaptic neurons. To evaluate this possibility, we have made a paired whole-cell recording from cultured hippocampal neurons with inhibitory synaptic connections. In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory neurotransmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca2+ concentration caused transient suppression of inhibitory synaptic currents, which is mainly due to reduction of GABA release. This depolarization-induced suppression was completely blocked by selective cannabinoid antagonists. Our results reveal that endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals to cause the reduction of transmitter release.
内源性大麻素被认为作为可扩散且作用短暂的调节剂发挥作用，其可能从突触后神经元向突触前神经元逆向传递信号。为评估这种可能性，我们对具有抑制性突触连接的培养海马神经元进行了配对全细胞记录。在约60%的配对中，大麻素激动剂极大地减少了突触前终末抑制性神经递质γ-氨基丁酸（GABA）的释放。在大多数此类配对中，但在那些对激动剂不敏感的配对中则不然，突触后神经元的去极化以及由此导致的细胞内钙离子浓度升高引起了抑制性突触电流的短暂抑制，这主要是由于GABA释放减少所致。这种去极化诱导的抑制被选择性大麻素拮抗剂完全阻断。我们的结果表明，内源性大麻素介导从去极化的突触后神经元到突触前终末的逆向信号，从而导致神经递质释放减少。
