Erythropoietin Induces Homeostatic Plasticity at Hippocampal Synapses
Erythropoietin Induces Homeostatic Plasticity at Hippocampal Synapses
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DOI：
10.1093/cercor/bhx159
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发表时间：
2018-08-01
期刊：
影响因子：
3.7
通讯作者：
Sebastiao, Ana M.
中科院分区：
文献类型：
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作者：
Dias, Raquel B.;Rodrigues, Tiago M.;Sebastiao, Ana M.
细胞因子促红细胞生成素（EPO）是红细胞生成的主要调节因子。有趣的是，许多研究表明，接受 EPO 的造血作用的患者的认知能力得到增强，这促使人们对使用基于 EPO 的策略来治疗神经精神疾病越来越感兴趣。 EPO 在大脑发育和成熟中发挥关键作用，但也调节突触传递。然而，后者背后的机制仍然难以捉摸。在这里，我们表明，急性（40-60 分钟）接触 EPO 突触前下调自发性和传入诱发的兴奋性传递，而不影响动作电位的基础放电。相反，长时间（3小时）接触EPO，如果随后有恢复期（1小时），能够引起兴奋性自发性的稳态增加，但不会引起诱发的突触传递。这些数据支持了新的观点，即分离的途径是自发和诱发的神经递质释放的基础。此外，我们发现，长时间接触 EPO 会促进海马长期增强，这种增强需要非常规地募集钙渗透性 AMPA 受体来维持。这些发现为 EPO 增强神经元功能、学习和记忆的机制提供了重要的新见解。
The cytokine erythropoietin (EPO) is the master regulator of erythropoiesis. Intriguingly, many studies have shown that the cognitive performance of patients receiving EPO for its hematopoietic effects is enhanced, which prompted the growing interest in the use of EPO-based strategies to treat neuropsychiatric disorders. EPO plays key roles in brain development and maturation, but also modulates synaptic transmission. However, the mechanisms underlying the latter have remained elusive. Here, we show that acute (40-60 min) exposure to EPO presynaptically downregulates spontaneous and afferent-evoked excitatory transmission, without affecting basal firing of action potentials. Conversely, prolonged (3 h) exposure to EPO, if followed by a recovery period (1 h), is able to elicit a homeostatic increase in excitatory spontaneous, but not in evoked, synaptic transmission. These data lend support to the emerging view that segregated pathways underlie spontaneous and evoked neurotransmitter release. Furthermore, we show that prolonged exposure to EPO facilitates a form of hippocampal long-term potentiation that requires noncanonical recruitment of calcium-permeable AMPA receptors for its maintenance. These findings provide important new insight into the mechanisms by which EPO enhances neuronal function, learning, and memory.