Mechanisms mediating effects of nitric oxide on perifornical lateral hypothalamic neurons.
Mechanisms mediating effects of nitric oxide on perifornical lateral hypothalamic neurons.
复制标题
一氧化氮对穹窿外侧下丘脑神经元影响的介导机制。
DOI：
10.1016/j.neuroscience.2012.06.014
复制
发表时间：
2012
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：
Kostin,A;McGinty,D;Szymusiak,R;Alam,MN
下丘脑穹窿周围外侧区（PF-LHA）是一个主要的促醒结构。它主要包含在行为和皮层激活期间活跃的神经元。一氧化氮（NO）是一种气态神经递质，与睡眠调节有关。最近，我们发现，在PF-LHA的NO水平较高，在持续清醒和NO发挥主要的抑制作用，特别是对PF-LHA神经元兴奋的触觉刺激。在本研究中，这种NO诱发的抑制作用的PF-LHA神经元的机制进行了评估。我们研究了腺苷能、GABA能和sGC-cGMP信号机制在介导氮能对PF-LHA神经元的影响中的作用。PF-LHA神经元的细胞外放电活动与微透析递送的药理学试剂相结合记录在麻醉大鼠中记录的神经元附近。首先，我们量化了阻断腺苷A1受体、GABAA受体和sGC-cGMP通路过程中PF-LHA神经元放电活动的变化。然后，我们确定了阻断腺苷A1受体、GABAA受体和sGC信号传导机制在减弱3，3-双（氨乙基）-1-羟基-1-氧代-1-三氮烯（一种NO供体）（NOC-18）（一种NO供体）对PF-LHA神经元放电活动的抑制作用中的功效。我们发现，NOC-18诱导的PF-LHA神经元放电活动的抑制在腺苷A1受体，GABAA受体和sGC-cGMP介导的信号传导阻断期间显著减弱。这些发现表明，一氧化氮诱发的PF-LHA神经元的抑制涉及一个复杂的机制，包括，但不限于，腺苷能，GABA能和sGC-cGMP信号通路。研究结果与PF-LHA内NO的普遍睡眠促进作用一致，并且鉴于该区域中腺苷能和GABA能系统的睡眠促进作用，进一步表明这种作用可能通过与其他神经递质和神经调质的氮能相互作用来介导。
The perifornical-lateral hypothalamic area (PF-LHA) is a major wake-promoting structure. It predominantly contains neurons that are active during behavioral and cortical activation. Nitric oxide (NO) is a gaseous neurotransmitter that has been implicated in the regulation of sleep. Recently we found that NO levels in the PF-LHA are higher during sustained waking and that NO exerts predominantly inhibitory effects, especially on PF-LHA neurons excited by tactile stimulation. The mechanisms underlying this NO-evoked inhibitory action on the PF-LHA neurons were assessed in the present study. We investigated the contributions of adenosinergic, GABAergic, and sGC-cGMP signaling mechanisms in mediating nitrergic influences on the PF-LHA neurons. The extracellular discharge activity of PF-LHA neurons was recorded in combination with microdialytic delivery of pharmacological agents adjacent to the recorded neurons in urethane-anesthetized rats. First, we quantified changes in the discharge activity of the PF-LHA neurons during the blockade of the adenosine A1receptor, GABAAreceptor, and sGC-cGMP pathway. Then, we determined the efficacy of blocking adenosine A1receptor, GABAAreceptor, and sGC signaling mechanisms in attenuating the inhibitory influences of 3,3-bis(aminoethyl)-1-hydroxy-1-oxo-1-triazene (a NO donor) (NOC-18), a NO donor, on the discharge activity of the PF-LHA neurons. We found that NOC-18-induced suppression in the discharge activity of PF-LHA neurons was significantly attenuated during the blockade of adenosine A1receptor-, GABAAreceptor-, and sGC-cGMP-mediated signaling. These findings suggest that NO-evoked inhibition of PF-LHA neurons involves a complex mechanism including, but may not be limited to, adenosinergic, GABAergic and sGC-cGMP signaling pathways. The findings are consistent with a generalized sleep-promoting role of NO within the PF-LHA and, given the sleep-promoting roles of adenosinergic and GABAergic systems in this area, further suggest that this effect may be mediated through nitrergic interactions with other neurotransmitters and neuromodulators.