Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Elife. 2017 Nov 15;6:e29688. doi: 10.7554/eLife.29688.
Hebbian plasticity is thought to require glutamate signalling. We show this is not the case for hippocampal presynaptic long-term potentiation (LTP), which is expressed as an increase in transmitter release probability (P). We find that LTP can be induced by pairing pre- and postsynaptic spiking in the absence of glutamate signalling. LTP induction involves a non-canonical mechanism of retrograde nitric oxide signalling, which is triggered by Ca influx from L-type voltage-gated Ca channels, not postsynaptic NMDA receptors (NMDARs), and does not require glutamate release. When glutamate release occurs, it decreases P by activating presynaptic NMDARs, and promotes presynaptic long-term depression. Net changes in P, therefore, depend on two opposing factors: (1) Hebbian activity, which increases P, and (2) glutamate release, which decreases P. Accordingly, release failures during Hebbian activity promote LTP induction. Our findings reveal a novel framework of presynaptic plasticity that radically differs from traditional models of postsynaptic plasticity.
赫伯氏可塑性被认为需要谷氨酸信号。我们表明，这不适用于海马体突触前长时程增强（LTP），后者表现为递质释放概率（P）的增加。我们发现，在没有谷氨酸信号的情况下，通过配对突触前和突触后放电可以诱导 LTP。LTP 的诱导涉及逆行一氧化氮信号的非经典机制，该机制由 L 型电压门控钙通道的钙内流触发，而不是由突触后 NMDA 受体（NMDAR）触发，并且不需要谷氨酸释放。当谷氨酸释放发生时，它通过激活突触前 NMDAR 来降低 P，并促进突触前长时程抑制。因此，P 的净变化取决于两个相反的因素：（1）赫伯氏活动，它增加 P，（2）谷氨酸释放，它降低 P。因此，赫伯氏活动期间的释放失败会促进 LTP 的诱导。我们的发现揭示了一种与传统的突触后可塑性模型截然不同的新型突触前可塑性框架。
