Neuropeptide Y modulates the electrical activity of subfornical organ neurons

Lauren Shute , Mark Fry
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Abstract

The subfornical organ (SFO) is a sensory circumventricular organ, lacking a blood-brain barrier. It is well-recognized as a key center for detection and integration of osmotic, ionic and hormonal signals for maintenance of hydromineral balance and cardiovascular regulation. Recently, the SFO has also been recognized as a center for the detection and integration of circulating satiety signals for regulation of energy balance. Neuropeptide Y (NPY) is a multifunctional neuropeptide, with effects on energy balance, cardiovascular tone and other aspects of homeostasis. Interestingly, despite the overlap of function between SFO and NPY, and observations that SFO expresses several subtypes of Y receptors, NPY regulation of SFO neurons has never been investigated. In this study, we examined the effects of NPY on dissociated rat SFO neurons using patch clamp electrophysiology. We observed that 300 nM NPY caused depolarization of 16 % of SFO neurons tested, and hyperpolarization of 26 %, while the remaining neurons were insensitive to NPY (n = 31). These effects were dose-dependent with an apparent EC50 of 3.9 nM for depolarizing neurons and 3.5 nM for hyperpolarizing neurons. Activation of Y5 receptors alone led to predominately hyperpolarizing effects, while activation of Y1 or Y2 receptors alone led to mixed responses. Voltage-clamp experiments demonstrated that NPY caused increases in voltage-gated K+ current amplitude as well as hyperpolarizing shifts in persistent Na+ current, mediating the hyperpolarizing and depolarizing effects, respectively. These findings indicate that NPY elicits direct electrophysiological effects on SFO neurons, suggesting that NPY acts via the SFO to regulate energy homeostatic function.

Abstract Image

神经肽Y调节皮层下器官神经元的电活动
皮层下器官(SFO)是一种感觉环绕心室的器官,缺乏血脑屏障。它被认为是检测和整合渗透、离子和激素信号的关键中心,用于维持水矿物质平衡和心血管调节。最近,SFO也被认为是检测和整合循环饱腹感信号以调节能量平衡的中心。神经肽Y (Neuropeptide Y, NPY)是一种多功能神经肽,对能量平衡、心血管张力等方面的内稳态都有影响。有趣的是,尽管SFO和NPY之间的功能重叠,并且观察到SFO表达几种Y受体亚型,但NPY对SFO神经元的调节从未被研究过。在这项研究中,我们使用膜片钳电生理学检测了NPY对游离大鼠SFO神经元的影响。我们观察到300 nM NPY导致16%的SFO神经元去极化,26%的SFO神经元超极化,而其余神经元对NPY不敏感(n = 31)。这些效应是剂量依赖性的,去极化神经元的EC50为3.9 nM,超极化神经元的EC50为3.5 nM。单独激活Y5受体导致主要的超极化效应,而单独激活Y1或Y2受体导致混合反应。电压箝位实验表明,NPY引起了电压门控K+电流幅值的增加以及持续Na+电流的超极化位移,分别介导了超极化和去极化效应。这些发现表明,NPY可以直接对SFO神经元产生电生理作用,表明NPY通过SFO调节能量稳态功能。
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CiteScore
2.20
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