Predominant Role of Serotonin at the Hippocampal Mossy Fiber Synapse with Redundant Monoaminergic Modulation
Predominant Role of Serotonin at the Hippocampal Mossy Fiber Synapse with Redundant Monoaminergic Modulation
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DOI：
10.1016/j.isci.2020.101025
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发表时间：
2020-04-24
期刊：
影响因子：
5.8
通讯作者：
Suzuki, Hidenori
中科院分区：
文献类型：
--
作者：
Kobayashi, Katsunori;Mikahara, Yasunori;Suzuki, Hidenori
海马苔藓纤维突触与精神疾病的病理生理学和治疗密切相关。该突触的多巴胺能和5-羟色胺能调节的改变是抗抑郁药物和其他相关治疗的候选机制。然而，这些单胺能调节在MF突触共享细胞内信号通路，这意味着它们的功能是冗余的。我们发现内源性单胺可以通过激活5-羟色胺5-HT4受体来增强小鼠海马片的MF突触传递。多巴胺受体不能被内源性激动剂有效激活，这表明多巴胺能调节是潜在的。电惊厥可增强5-HT4受体介导的突触5-HT4能突触增强作用，增加海马5-羟色胺含量，并以5-HT4受体依赖的方式产生抗焦虑的行为效应。这些结果表明，5-羟色胺在MF突触的单胺能调节中起主导作用。这种5-羟色胺能调节的增强可能介导了电惊厥治疗的抗焦虑作用。
The hippocampal mossy fiber (MF) synapse has been implicated in the pathophysiology and treatment of psychiatric disorders. Alterations of dopaminergic and serotonergic modulations at this synapse are candidate mechanisms underlying antidepressant and other related treatments. However, these monoaminergic modulations share the intracellular signaling pathway at the MF synapse, which implies redundancy in their functions. We here show that endogenous monoamines can potentiate MF synaptic transmission in mouse hippocampal slices by activating the serotonin 5-HT4 receptor. Dopamine receptors were not effectively activated by endogenous agonists, suggesting that the dopaminergic modulation is latent. Electroconvulsive treatment enhanced the 5-HT4 receptor-mediated serotonergic synaptic potentiation specifically at the MF synapse, increased the hippocampal serotonin content, and produced an anxiolytic-like behavioral effect in a 5-HT4 receptor-dependent manner. These results suggest that serotonin plays a predominant role in monoaminergic modulations at the MF synapse. Augmentation of this serotonergic modulation may mediate anxiolytic effects of electroconvulsive treatment.