A1 receptor mediated adenosinergic regulation of perifornical-lateral hypothalamic area neurons in freely behaving rats.
A1 receptor mediated adenosinergic regulation of perifornical-lateral hypothalamic area neurons in freely behaving rats.
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DOI：
10.1016/j.neuroscience.2010.01.044
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发表时间：
2010-04-28
期刊：
影响因子：
3.3
通讯作者：
Alam MN
中科院分区：
文献类型：
--
作者：
Rai S;Kumar S;Alam MA;Szymusiak R;McGinty D;Alam MN
穹隆周围-外侧下丘脑区(PF-LHA)在行为觉醒的调节中起着重要作用。PF-LHA包含几种神经元类型，包括觉醒活性下丘脑素(HCRT)神经元，这些神经元与促进和/或维持行为唤醒有关。腺苷是一种内源性睡眠因子，最近的证据表明，激活和阻断PF-LHA内的腺苷A1受体分别促进和抑制睡眠。虽然体外研究表明腺苷通过A1受体抑制HCRT神经元，但A1受体介导的腺苷能传递对包括HCRT神经元在内的PF-LHA神经元的体内影响尚不清楚。首先，我们测定了腺苷A1受体激动剂N6-环戊基腺苷(CPA)对Pf-LHA神经元睡眠觉醒放电活动的影响，该活动是通过放置在微透析探针旁边的微丝记录的。其次，我们测定了CPA和A1受体拮抗剂1，3-二丙基-8-苯基黄嘌呤(CPDX)进入PF-LHA对HCRT和微透析探针周围非HCRT神经元CFos蛋白免疫反应性(Fos-IR)的影响。CPA的作用是在熄灯阶段保持清醒的大鼠身上进行的，而CPDX的作用是在正常大鼠的点灯阶段进行的。CPA显著抑制Pf-LHA神经元的睡眠-觉醒放电活动。在我们早期的研究中，分别抑制和诱导觉醒的CPA(50μM)和CPDX(50μM)剂量显著抑制和增加了HCRT和非HCRT神经元的Fos-IR。这些发现表明，促进觉醒的PF-LHA系统受到内源性腺苷能抑制的增加，腺苷通过A1受体作用，部分地抑制了HCRT神经元促进睡眠。
The perifornical-lateral hypothalamic area (PF-LHA) plays a central role in the regulation of behavioral arousal. The PF-LHA contains several neuronal types including wake-active hypocretin (HCRT) neurons that have been implicated in the promotion and/or maintenance of behavioral arousal. Adenosine is an endogenous sleep factor and recent evidence suggests that activation and blockade of adenosine A1 receptors within the PF-LHA promote and suppress sleep, respectively. Although, an in vitro study indicates that adenosine inhibits HCRT neurons via A1 receptor, the in vivo effects of A1 receptor mediated adenosinergic transmission on PF-LHA neurons including HCRT neurons are not known. First, we determined the effects of N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, on the sleep-wake discharge activity of the PF-LHA neurons recorded via microwires placed adjacent to the microdialysis probe used for its delivery. Second, we determined the effects of CPA and that of an A1 receptor antagonist, 1,3-dipropyl-8-phenylxanthine (CPDX) into the PF-LHA on cFos-protein immunoreactivity (Fos-IR) in HCRT and non-HCRT neurons around the microdialysis probe used for their delivery. The effect of CPA was studied in rats that were kept awake during lights-off phase, whereas the effect of CPDX was examined in undisturbed rats during lights-on phase. CPA significantly suppressed the sleep-wake discharge activity of PF-LHA neurons. Doses of CPA (50μM) and CPDX (50μM) that suppressed and induced arousal, respectively, in our earlier study, significantly suppressed and increased Fos-IR in HCRT and non-HCRT neurons. These findings suggest that wake-promoting PF-LHA system is subject to increased endogenous adenosinergic inhibition and that adenosine acting via A1 receptors, in part, inhibits HCRT neurons to promote sleep.
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