Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity
Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity
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DOI：
10.1111/j.1460-9568.2011.07631.x
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发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Fuenzalida, Marco
中科院分区：
文献类型：
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作者：
Bonansco, Christian;Couve, Alejandro;Fuenzalida, Marco
在大鼠海马脑片中，星形胶质细胞表现出自发性钙振荡，这种自发性钙振荡可诱导谷氨酸释放。然而，这是未知的星形胶质细胞谷氨酸的自发释放是否可能有助于确定在中枢突触的基础神经递质释放的概率。利用全细胞记录和钙离子成像技术，我们研究了星形胶质细胞自发活动对CA 3-CA 1海马突触神经传递和突触可塑性的影响。我们在这里表明，代谢性胶毒素氟柠檬酸（FC）降低诱发兴奋性突触后电流的幅度，增加成对脉冲易化，主要是由于神经递质释放概率和突触效能的降低。FC还降低星形胶质细胞的细胞内Ca 2+信号和Ca 2+依赖的谷氨酸释放。谷氨酰胺的加入挽救了FC对突触效能的影响;然而，神经递质释放的可能性仍然减少。I组代谢型谷氨酸受体的阻断模仿FC对微型突触反应频率的影响。在FC、钙离子螯合剂1，2-双（2-氨基苯氧基）乙烷-N，N，N '，N '-四乙酸酯或I组代谢型谷氨酸受体拮抗剂存在下，由尖峰时间依赖性可塑性方案诱导的兴奋性突触后电流增强被阻断，并通过提供更强的尖峰时间依赖性可塑性方案来拯救。两者合计，这些结果表明，从星形胶质细胞的自发谷氨酸释放有助于通过代谢型谷氨酸受体激活，这可能是作为一个增益控制机制，调节长时程增强的阈值设置神经递质释放的基础概率。因此，内源性星形胶质细胞活性提供了一种新的非神经元机制，可能是关键的中枢神经系统中的信息传递。
Astrocytes exhibit spontaneous calcium oscillations that could induce the release of glutamate as gliotransmitter in rat hippocampal slices. However, it is unknown whether this spontaneous release of astrocytic glutamate may contribute to determining the basal neurotransmitter release probability in central synapses. Using whole-cell recordings and Ca2+ imaging, we investigated the effects of the spontaneous astrocytic activity on neurotransmission and synaptic plasticity at CA3-CA1 hippocampal synapses. We show here that the metabolic gliotoxin fluorocitrate (FC) reduces the amplitude of evoked excitatory postsynaptic currents and increases the paired-pulse facilitation, mainly due to the reduction of the neurotransmitter release probability and the synaptic potency. FC also decreased intracellular Ca2+ signalling and Ca2+-dependent glutamate release from astrocytes. The addition of glutamine rescued the effects of FC over the synaptic potency; however, the probability of neurotransmitter release remained diminished. The blockage of group I metabotropic glutamate receptors mimicked the effects of FC on the frequency of miniature synaptic responses. In the presence of FC, the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetra-acetate or group I metabotropic glutamate receptor antagonists, the excitatory postsynaptic current potentiation induced by the spike-timing-dependent plasticity protocol was blocked, and it was rescued by delivering a stronger spike-timing-dependent plasticity protocol. Taken together, these results suggest that spontaneous glutamate release from astrocytes contributes to setting the basal probability of neurotransmitter release via metabotropic glutamate receptor activation, which could be operating as a gain control mechanism that regulates the threshold of long-term potentiation. Therefore, endogenous astrocyte activity provides a novel non-neuronal mechanism that could be critical for transferring information in the central nervous system.