University of California, San Francisco, Physiology Department, CA, USA.
Allen Institute for Brain Science, Seattle, WA 98103, USA.
Curr Opin Neurobiol. 2018 Aug;51:1-7. doi: 10.1016/j.conb.2017.12.020. Epub 2018 Jan 30.
In the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian plasticity via Ca influx. However, unconventional presynaptic NMDARs (preNMDARs) which regulate both long-term and short-term plasticity at several synapse types have also been found. A lack of sufficiently specific experimental manipulations and a poor understanding of how preNMDARs signal have contributed to long-standing controversy surrounding these receptors. Although several prior studies linked preNMDARs to neocortical timing-dependent long-term depression (tLTD), a recent study argues that the NMDARs are actually postsynaptic and signal metabotropically, that is, without Ca. Other recent work indicates that, whereas ionotropic preNMDARs signaling controls evoked release, spontaneous release is regulated by metabotropic NMDAR signaling. We argue that elucidating unconventional NMDAR signaling modes-both presynaptically and metabotropically-is key to resolving the preNMDAR debate.
在经典观点中，突触后 NMDA 受体（NMDAR）通过 Ca 内流触发赫伯氏型可塑性。然而，已经发现了几种突触类型的非常规突触前 NMDAR（preNMDAR），它们调节长时程和短时程可塑性。缺乏足够特异的实验操作以及对 preNMDAR 信号的理解不足，导致了围绕这些受体的长期争议。尽管先前的几项研究将 preNMDAR 与新皮层时依赖型长时程抑制（tLTD）联系起来，但最近的一项研究认为，NMDAR 实际上是突触后的，并且是代谢型信号传递的，也就是说，没有 Ca。最近的其他研究表明，虽然离子型 preNMDAR 信号控制诱发释放，但自发释放由代谢型 NMDAR 信号调节。我们认为，阐明非传统的 NMDAR 信号传递模式——无论是突触前还是代谢型——是解决 preNMDAR 争议的关键。
