Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus
Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus
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DOI：
10.1523/jneurosci.0314-14.2015
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发表时间：
2015-04-22
影响因子：
5.3
通讯作者：
Contractor, Anis
中科院分区：
文献类型：
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作者：
Fernandes, Herman B.;Riordan, Sean;Contractor, Anis
突触前终末cAMP升高在海马苔藓纤维-CA 3突触的可塑性中起核心作用。先前的研究已经确定蛋白激酶A作为cAMP的下游效应物，其有助于苔藓纤维LTP（MF-LTP），但是在MF突触中表达的另一种cAMP效应物Epac 2的潜在贡献尚未被考虑。我们使用Epac 2（-/-）小鼠研究了Epac 2在MF-CA 3神经传递中的作用。Epac 2的缺失不会引起海马神经解剖学或基础突触传递的总体改变。突触促进在短期列车的Epac 2活性的损失没有受到影响，但是，长期的可塑性和毛喉素介导的增强MF受损，表明Epac 2有助于cAMP依赖性增强的递质释放。在长时间持续的活动过程中对突触传递的检查表明，Epac 2（-/-）小鼠中容易释放的囊泡池减少。这些数据表明，cAMP升高使用Epac 2依赖性途径来促进递质释放，并且Epac 2是维持海马中MF突触处的易释放池所必需的。
Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2(-/-) mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2(-/-) mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus.