Roles of phospholipase Cβ and NMDA receptor in activity-d epen dent endocannabinoid release
Roles of phospholipase Cβ and NMDA receptor in activity-d epen dent endocannabinoid release
复制标题
DOI：
10.1113/jphysiol.2007.137497
复制
发表时间：
2007-10-15
影响因子：
5.5
通讯作者：
Kano, Masanobu
中科院分区：
文献类型：
--
作者：
Hashimotodani, Yuki;Ohno-Shosaku, Takako;Kano, Masanobu
内源性大麻素从突触后神经元释放，激活突触前大麻素受体，并在整个大脑中引起各种形式的短期和长期突触可塑性。使用海马和小脑神经元，我们已经发现，内源性大麻素的释放可以通过两种不同的途径诱导。一种是独立于磷脂酶C，3（PLC，3）和单独由Ca 2+升高驱动（Ca 2+驱动的内源性大麻素释放，CaER），另一种是PLC β依赖性和G（q/11）偶联受体的激活驱动（受体驱动的内源性大麻素释放，RER）。CaER通过激活电压门控Ca 2+通道或NMDA受体诱导。RER即使在静息Ca 2+水平（基础RER）下也是有功能的，但通过小的Ca 2+升高（Ca 2+辅助RER）显着增强。在Ca 2+辅助的RER中，PLC β作为受体激活和Ca 2+升高的符合检测器。我们还表明，钙离子辅助RER是必要的内源性大麻素释放触发突触活动。我们的解剖学数据表明，RER所需的一组受体和酶组织良好，使兴奋性输入可以有效地触发RER。据报道，某些形式的尖峰时间依赖性可塑性（STDP）依赖于内源性大麻素信号传导。NMDA受体和PLC，3可能发挥关键作用的内源性大麻素依赖性形式的STDP作为符合探测器具有不同的时间依赖性。
Endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid receptors and cause various forms of short-term and long-term synaptic plasticity throughout the brain. Using hippocampal and cerebellar neurons, we have revealed that endocannabinoid release can be induced through two different pathways. One is independent of phospholipase C,3 (PLC,3) and driven by Ca2+ elevation alone (Ca2+-driven endocannabinoid release, CaER), and the other is PLC beta-dependent and driven by activation of G(q/11)-coupled receptors (receptor-driven endocannabinoid release, RER). CaER is induced by activation of either voltage-gated Ca2+ channels or NMDA receptors. RER is functional even at resting Ca2+ levels (basal RER), but markedly enhanced by a small Ca2+ elevation (Ca2+-assisted RER). In Ca2+-assisted RER, PLC beta serves as a coincidence detector of receptor activation and Ca2+ elevation. We have also demonstrated that Ca2+-assisted RER is essential for the endocannabinoid release triggered by synaptic activity. Our anatomical data show that a set of receptors and enzymes required for RER are well organized so that the excitatory input can trigger RER effectively. Certain forms of spike-timing-dependent plasticity (STDP) are reported to depend on endocannabinoid signalling. The NMDA receptor and PLC,3 might play key roles in the endocannabinoid-dependent forms of STDP as coincidence detectors with different timing dependences.