GABA-mediated control of hypocretin- but not melanin-concentrating hormone-immunoreactive neurones during sleep in rats
GABA-mediated control of hypocretin- but not melanin-concentrating hormone-immunoreactive neurones during sleep in rats
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DOI：
10.1113/jphysiol.2004.076927
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发表时间：
2005-03-01
影响因子：
5.5
通讯作者：
McGinty, D
中科院分区：
文献类型：
--
作者：
Alam, MN;Kumar, S;McGinty, D
下丘脑周围外侧区（PF-LHA）与行为唤醒的调节有关。 PF-LHA 包含多种细胞类型，包括表达肽、下丘脑分泌素 (HCRT；也称为食欲素) 和黑色素浓缩激素 (MCH) 的神经元。有证据表明，大多数 PF-LHA 神经元（包括 HCRT 神经元）在清醒时活跃，在非快速眼动 (non-NREM) 睡眠期间静止。 PF-LHA 包含局部 GABA 能中间神经元，还接收来自下丘脑视前区促进睡眠区域的 GABA 能输入。我们假设 PF-LHA 内 GABA 介导的抑制作用增加有助于抑制非快速眼动睡眠期间的神经元活动。在开灯期间，将人工脑脊液（aCSF）或荷包牡丹碱（一种 GABA（A）受体拮抗剂）微透析输送到自发睡眠的大鼠的 PF-LHA 中，对大鼠的 EEG 和 EMG 活动进行 2 小时的监测。在aCSF或荷包牡丹碱灌注结束时，处死大鼠并对HCRT、MCH和其他PF-LHA神经元中的c-Fos免疫反应性(Fos-IR)进行定量。荷包牡丹碱灌注到 PF-LHA 后，大鼠表现出非快速眼动和快速眼动睡眠时间的剂量依赖性减少以及清醒时间的增加。与微透析探针相邻的表现出 Fos-IR 的 HCRT、MCH 和非 HCRT/非 MCH 神经元的数量也响应荷包牡丹碱而剂量依赖性增加。然而，与 HCRT 和其他 PF-LHA 神经元相比，对荷包牡丹碱反应表现出 Fos-IR 的 MCH 神经元明显较少。这些结果支持这样的假设：PF-LHA 神经元，包括 HCRT 神经元，在睡眠期间受到内源性 GABA 能抑制增加的影响。相比之下，MCH 神经元在睡眠期间似乎受到较弱的 GABA 控制。
The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of behavioural arousal. The PF-LHA contains several cell types including neurones expressing the peptides, hypocretin (HCRT; also called orexin) and melanin-concentrating hormone (MCH). Evidence suggests that most of the PF-LHA neurones, including HCRT neurones, are active during waking and quiescent during non-rapid eye movement (non-NREM) sleep. The PF-LHA contains local GABAergic interneurones and also receives GABAergic inputs from sleep-promoting regions in the preoptic area of the hypothalamus. We hypothesized that increased GABA-mediated inhibition within PF-LHA contributes to the suppression of neuronal activity during non-REM sleep. EEG and EMG activity of rats were monitored for 2 h during microdialytic delivery of artificial cerebrospinal fluid (aCSF) or bicuculline, a GABA(A) receptor antagonist, into the PF-LHA in spontaneously sleeping rats during the lights-on period. At the end of,,aCSF or bicuculline perfusion, rats were killed and c-Fos immunoreactivity (Fos-IR) in HCRT, MCH and other PF-LHA neurones was quantified. In response to bicuculline perfusion into the PF-LHA, rats exhibited a dose-dependent decrease in non-REM and REM sleep time and an increase in time awake. The number of HCRT, MCH and non-HCRT/non-MCH neurones exhibiting Fos-IR adjacent to the microdialysis probe also increased dose-dependently in response to bicuculline. However, significantly fewer MCH neurones exhibited Fos-IR in response to bicuculline as compared to HCRT and other PF-LHA neurones. These results support the hypothesis that PF-LHA neurones, including HCRT neurones, are subject to increased endogenous GABAergic inhibition during sleep. In contrast, MCH neurones appear to be subject to weaker GABAergic control during sleep.