Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals

Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals
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DOI:
10.1016/s0896-6273(01)00247-1
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发表时间:
2001-03-01
期刊:
影响因子:
16.2
通讯作者:
Kano, M
Kano, M
中科院分区:
医学1区
文献类型:
--
作者:
Ohno-Shosaku, T;Maejima, T;Kano, M

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内源性大麻素被认为是一种可扩散的、短暂的调节剂,可以将信号从突触后逆行传递到突触前神经元。为了评估这种可能性,我们对培养的具有抑制性突触连接的海马神经元进行了配对的全细胞记录。在大约60%的神经对中,大麻类激动剂极大地减少了从突触前终末释放的抑制性神经递质GABA。在大多数突触后神经元中,突触后神经元的去极化和由此引起的细胞内钙离子浓度的升高导致抑制性突触电流的一过性抑制,这主要是由于GABA释放的减少。这种去极化诱导的抑制可被选择性大麻素拮抗剂完全阻断。我们的结果表明,内源性大麻素将去极化的突触后神经元的逆行信号传递到突触前终末,导致递质释放减少。
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.