Estradiol acutely potentiates hippocampal excitatory synaptic transmission through a presynaptic mechanism.
Estradiol acutely potentiates hippocampal excitatory synaptic transmission through a presynaptic mechanism.
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DOI：
10.1523/jneurosci.4161-10.2010
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发表时间：
2010-12-01
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影响因子：
--
通讯作者：
Woolley CS
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文献类型：
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作者：
Smejkalova T;Woolley CS
虽然最近的证据表明海马是17β-雌二醇（E2）的来源，但与卵巢E2不同，这种神经类固醇E2的生理作用尚不清楚。神经类固醇E2的一个可能功能是急性增强兴奋性突触传递，但这种作用的机制尚不清楚。利用全细胞电压钳记录成年大鼠海马切片中突触诱发的EPSCs，我们发现，与早期研究的结论相反，E2通过突触前机制增强兴奋性传递。我们发现E2通过增加谷氨酸释放的概率来增强EPSCs，特别是在低初始释放概率的输入。这种作用是由雌激素受体(ER)β作为单体介导的，而ERα则不是必需的。我们进一步表明，e2诱导谷氨酸释放增加主要是由于个体囊泡释放概率增加，并与谷氨酸平均浓度升高有关。这两项研究结果共同有力地证明了E2促进多泡释放，这在成人海马体中从未被证实过。急性EPSC增强的快速时间过程及其浓度依赖性表明，局部合成的神经类固醇E2可能在体内激活这种作用。
While recent evidence suggests that the hippocampus is a source of 17β-estradiol (E2), the physiological role of this neurosteroid E2, as distinct from ovarian E2, is unknown. One likely function of neurosteroid E2 is to acutely potentiate excitatory synaptic transmission, but the mechanism of this effect is not well understood. Using whole-cell voltage-clamp recording of synaptically evoked EPSCs in adult rat hippocampal slices, we show that, in contrast to the conclusions of earlier studies, E2 potentiates excitatory transmission through a presynaptic mechanism. We find that E2 acutely potentiates EPSCs by increasing the probability of glutamate release specifically at inputs with low initial release probability. This effect is mediated by estrogen receptor (ER)β acting as a monomer, whereas ERα is not required. We further show that the E2-induced increase in glutamate release is due primarily to increased individual vesicle release probability and is associated with higher average cleft glutamate concentration. These two findings together argue strongly that E2 promotes multivesicular release, which has not been shown before in the adult hippocampus. The rapid time course of acute EPSC potentiation and its concentration dependence suggest that locally-synthesized neurosteroid E2 may activate this effect in vivo.