Associative short-term synaptic plasticity mediated by endocannabinoids
Associative short-term synaptic plasticity mediated by endocannabinoids
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DOI：
10.1016/j.neuron.2004.12.045
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发表时间：
2005-02-03
期刊：
影响因子：
16.2
通讯作者：
Regehr, WG
中科院分区：
文献类型：
--
作者：
Brenowitz, SD;Regehr, WG
联想学习在快速时间尺度上很重要，但没有合适的形式的短期可塑性已被确定，这是联想和突触特异性。在这里，我们评估内源性大麻素是否可以介导这种可塑性。在小脑中，平行纤维（PF）活动的爆发引起浦肯野细胞树突释放内源性大麻素，导致持续数秒的逆行突触抑制。我们发现，强大的攀爬纤维（CF）浦肯野细胞突触调节这种抑制。与单独的PF刺激相比，PF和CF突触的共激活大大增强了内源性大麻素介导的PF突触抑制。逆行抑制仅限于CF激活后几百毫秒内激活的PF。这种关联可塑性反映了钙依赖性内源性大麻素释放的两个方面。首先，PF介导的代谢型谷氨酸受体的激活局部降低了内源性大麻素释放所需的树突钙水平。第二，CF和PF共激活诱发局部超线性树突状钙信号。因此，内源性大麻素介导瞬时关联突触可塑性。
Associative learning is important on rapid timescales, but no suitable form of short-term plasticity has been identified that is both associative and synapse specific. Here, we assess whether endocannabinoids can mediate such plasticity. In the cerebellum, bursts of parallel fiber (PF) activity evoke endocannabinoid release from Purkinje cell dendrites that results in retrograde synaptic inhibition lasting seconds. We find that the powerful climbing fiber (CF) to Purkinje cell synapse regulates this inhibition. Compared to PF stimulation alone, coactivation of PF and CF synapses greatly enhanced endocannabinoid-mediated inhibition of PF synapses. Retrograde inhibition was restricted to PFs activated within several hundred milliseconds of CF activation. This associative plasticity reflects two aspects of calcium-dependent endocannabinoid release. First, PF-mediated activation of metabotropic glutamate receptors locally reduced the dendritic calcium levels required for endocannabinoid release. Second, CF and PF coactivation evoked localized supralinear dendritic calcium signals. Thus, endocannabinoids mediate transient associative synaptic plasticity.