Endocannabinoids Potentiate Synaptic Transmission through Stimulation of Astrocytes
Endocannabinoids Potentiate Synaptic Transmission through Stimulation of Astrocytes
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DOI：
10.1016/j.neuron.2010.08.043
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发表时间：
2010-10-07
期刊：
影响因子：
16.2
通讯作者：
Araque, Alfonso
中科院分区：
文献类型：
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作者：
Navarrete, Marta;Araque, Alfonso
内源性大麻素及其受体CB 1在脑功能中起着关键作用。星形胶质细胞表达被神经元释放的内源性大麻素激活的CB 1 R。然而，内源性大麻素介导的神经元-星形胶质细胞信号传导对突触传递的影响尚不清楚。我们发现，海马锥体神经元释放的内源性大麻素增加了CA 3-CA 1突触释放递质的概率。这种突触增强是由于CB 1 R诱导的星形胶质细胞中的Ca 2+升高，其刺激谷氨酸的释放，从而激活突触前代谢型谷氨酸受体。虽然内源性大麻素通过直接激活突触前CB 1 Rs在受刺激的神经元中诱导突触抑制，但它们通过激活星形胶质细胞中的CB 1 Rs间接导致相对更远的神经元中的突触增强。因此，由内源性刺激（神经元释放的内源性大麻素）引起的星形胶质细胞钙信号调节突触传递。因此，星形胶质细胞对内源性大麻素产生反应，然后增强突触传递，表明星形胶质细胞积极参与脑生理学。
Endocannabinoids and their receptor CB1 play key roles in brain function. Astrocytes express CB1 Rs that are activated by endocannabinoids released by neurons. However, the consequences of the endocannabinoid-mediated neuron-astrocyte signaling on synaptic transmission are unknown. We show that endocannabinoids released by hippocampal pyramidal neurons increase the probability of transmitter release at CA3-CA1 synapses. This synaptic potentiation is due to CB1R-induced Ca2+ elevations in astrocytes, which stimulate the release of glutamate that activates presynaptic metabotropic glutamate receptors. While endocannabinoids induce synaptic depression in the stimulated neuron by direct activation of presynaptic CB1 Rs, they indirectly lead to synaptic potentiation in relatively more distant neurons by activation of CB1 Rs in astrocytes. Hence, astrocyte calcium signal evoked by endogenous stimuli (neuron-released endocannabinoids) modulates synaptic transmission. Therefore, astrocytes respond to endocannabinoids that then potentiate synaptic transmission, indicating that astrocytes are actively involved in brain physiology.