Zhang Bin-Bin, Jin Hua, Bing Yan-Hua, Zhang Xin-Yuan, Chu Chun-Ping, Li Yu-Zi, Qiu De-Lai
Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, China.
Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China.
Front Cell Neurosci. 2019 Jun 27;13:283. doi: 10.3389/fncel.2019.00283. eCollection 2019.
The magnocellular neurosecretory cells (MNCs) of the hypothalamic paraventricular nucleus (PVN) integrate incoming signals to secrete oxytocin (OT), and vasopressin (VP) from their nerve terminals in the posterior pituitary gland. In the absence of gamma-aminobutyric acid A (GABA) and cannabinoids 1 (CB1) receptor activity, we used whole-cell patch-clamp recording, single-cell reverse transcription-multiplex polymerase chain reaction (SC-RT-mPCR), biocytin histochemistry and pharmacological methods to examine the mechanism of high frequency stimulus (HFS, 100 Hz)-induced long-term potentiation (LTP) at glutamatergic synapses in the PVN MNCs of juvenile male rats. Our results showed that HFS-induced LTP at glutamatergic synapses was accompanied by a decrease in the paired-pulse ratio (PPR) of the PVN MNCs. In these MNCs, HFS-induced LTP persisted in the presence of a group 1 metabotropic glutamate receptor (mGluR1) antagonist; however, it was abolished by an -methyl-D-aspartic acid (NMDA) receptor blocker. Notably, HFS-induced LTP in the PVN MNCs was completely prevented by a nitric oxide synthase (NOS) inhibitor. The application of an NO donor not only induced the LTP of excitatory glutamatergic inputs in the PVN MNCs, but also occluded the HFS-induced LTP in these MNCs. Moreover, HFS-induced LTP in the PVN MNCs was also abolished by a specific protein kinase A (PKA) inhibitor, KT5720. SC-RT-mPCR analysis revealed that 64.5% (62/96) of MNCs expressed OT mRNA. Our results indicate that a HFS can induce an NMDA receptor and NO cascades dependent on presynaptic glutamatergic LTP in the PVN MNCs via a PKA signaling pathway.
下丘脑室旁核（PVN）的大细胞神经分泌细胞（MNCs）整合传入信号，从其位于垂体后叶的神经末梢分泌催产素（OT）和血管加压素（VP）。在缺乏γ-氨基丁酸A（GABA）和大麻素1（CB1）受体活性的情况下，我们使用全细胞膜片钳记录、单细胞逆转录-多重聚合酶链反应（SC-RT-mPCR）、生物素组织化学和药理学方法，研究了高频刺激（HFS，100 Hz）诱导幼年雄性大鼠PVN MNCs谷氨酸能突触长时程增强（LTP）的机制。我们的结果表明，HFS诱导的谷氨酸能突触LTP伴随着PVN MNCs配对脉冲比率（PPR）的降低。在这些MNCs中，HFS诱导的LTP在I组代谢型谷氨酸受体（mGluR1）拮抗剂存在的情况下持续存在；然而，它被N-甲基-D-天冬氨酸（NMDA）受体阻滞剂消除。值得注意的是，HFS诱导的PVN MNCs中的LTP被一氧化氮合酶（NOS）抑制剂完全阻断。应用NO供体不仅诱导了PVN MNCs中兴奋性谷氨酸能输入的LTP，而且还阻断了这些MNCs中HFS诱导的LTP。此外，HFS诱导的PVN MNCs中的LTP也被特异性蛋白激酶A（PKA）抑制剂KT5720消除。SC-RT-mPCR分析显示，64.5%（62/96）的MNCs表达OT mRNA。我们的结果表明，HFS可通过PKA信号通路在PVN MNCs中诱导依赖于突触前谷氨酸能LTP的NMDA受体和NO级联反应。
