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食欲素A在突触前降低大鼠蓝斑核神经元的抑制性突触传递。

Orexin A presynaptically decreases inhibitory synaptic transmission in rat locus coeruleus neurons.

作者信息

Kargar Hossein Mohammad-Pour, Azizi Hossein, Mirnajafi-Zadeh Javad, Mani Ali Reza, Semnanian Saeed

机构信息

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Biology, Faculty of Sciences, Islamjc Azad University, Damghan branch, Damghan, Iran.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Neurosci Lett. 2018 Sep 14;683:89-93. doi: 10.1016/j.neulet.2018.06.022. Epub 2018 Jun 13.

Abstract

Locus coeruleus nucleus (LC) is a major noradrenergic nucleus in the brain. It receives dense orexinergic projections from lateral hypothalamus. Whilst it is known that orexin A increases firing rate of LC neurons, its effect on spontaneous and evoked inhibitory postsynaptic currents (sIPSCs and eIPSCs, respectively) has not been yet identified. In this research, we investigated the effect of orexin A on eIPSCs and sIPSCs in LC neurons. Whole-cell recordings revealed that orexin A suppresses eIPSCs amplitude in which this effect was blocked by an orexin type-1 receptors antagonist (SB-334867) and cannabinoid type-1 (CB1) receptors antagonist (AM251). Moreover, exposure of neurons to BAPTA (Ca chelator) and U73122 (phospholipase C inhibitor) prevented orexin A-induced eIPSCs depression. On the other hand, orexin A increased pair pulse ratio and sIPSCs frequency but had no effect on sIPSCs amplitude. Our results revealed that eIPSCs suppression in the LC is mediated by CB1 receptor through a presynaptic mechanism.

摘要

蓝斑核(LC)是大脑中主要的去甲肾上腺素能核团。它接受来自下丘脑外侧的密集的食欲素能投射。虽然已知食欲素A会增加LC神经元的放电频率,但其对自发和诱发的抑制性突触后电流(分别为sIPSCs和eIPSCs)的影响尚未明确。在本研究中,我们研究了食欲素A对LC神经元中eIPSCs和sIPSCs的影响。全细胞记录显示,食欲素A会抑制eIPSCs的幅度,其中这种作用被食欲素1型受体拮抗剂(SB - 334867)和大麻素1型(CB1)受体拮抗剂(AM251)所阻断。此外,将神经元暴露于BAPTA(钙螯合剂)和U73122(磷脂酶C抑制剂)可防止食欲素A诱导的eIPSCs抑制。另一方面,食欲素A增加了双脉冲比率和sIPSCs频率,但对sIPSCs幅度没有影响。我们的结果表明,LC中eIPSCs的抑制是由CB1受体通过突触前机制介导的。

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