Kobayashi Katsunori, Mikahara Yasunori, Murata Yuka, Morita Daiki, Matsuura Sumire, Segi-Nishida Eri, Suzuki Hidenori
Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
iScience. 2020 Apr 24;23(4):101025. doi: 10.1016/j.isci.2020.101025. Epub 2020 Mar 31.
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-HT receptor. Dopamine receptors were not effectively activated by endogenous agonists, suggesting that the dopaminergic modulation is latent. Electroconvulsive treatment enhanced the 5-HT 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-HT 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.
海马苔藓纤维（MF）突触与精神疾病的病理生理学及治疗有关。该突触处多巴胺能和5-羟色胺能调制的改变是抗抑郁及其他相关治疗的潜在机制。然而，这些单胺能调制在MF突触共享细胞内信号通路，这意味着它们功能上存在冗余。我们在此表明，内源性单胺可通过激活5-羟色胺5-HT受体增强小鼠海马切片中的MF突触传递。内源性激动剂不能有效激活多巴胺受体，提示多巴胺能调制处于潜伏状态。电休克治疗特异性增强了MF突触处5-HT受体介导的5-羟色胺能突触增强，增加了海马5-羟色胺含量，并以5-HT受体依赖的方式产生抗焦虑样行为效应。这些结果表明，5-羟色胺在MF突触的单胺能调制中起主要作用。这种5-羟色胺能调制的增强可能介导电休克治疗的抗焦虑效应。
