Opioids prolong and anoxia shortens delay between onset of preinspiratory (pFRG) and inspiratory (preBotC) network bursting in newborn rat brainstems
Opioids prolong and anoxia shortens delay between onset of preinspiratory (pFRG) and inspiratory (preBotC) network bursting in newborn rat brainstems
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DOI：
10.1007/s00424-009-0645-3
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发表时间：
2009-07-01
影响因子：
4.5
通讯作者：
Onimaru, H.
中科院分区：
文献类型：
--
作者：
Ballanyi, K.;Ruangkittisakul, A.;Onimaru, H.
对阿片类药物的不同反应建立了一个假设，即面旁呼吸组（pFRG）的吸气前/吸气后（Pre-I）神经元和前Botzinger复合体（preBotC）的吸气（Insp）神经元构成了双脑干呼吸中心。为了进一步分析pFRG/preBotC相互作用，我们研究了新生大鼠脑干脊髓制剂阿片和缺氧对组织学鉴定的pFRG驱动的“I型”Insp preBotC神经元和来自三个不同呼吸脑干区域的Pre-I神经元的影响。μ-阿片样物质[D-Ala（2），N-Me-Phe（4），Gly（5）-ol]-脑啡肽（DAMGO）可定量减慢吸气相关的颈神经爆发，而缺氧则可诱导非定量减慢和重复的颈神经爆发。DAMGO对Pre-I神经元的膜电位和输入电阻没有影响，而缺氧使其超极化（约5 mV），电阻降低（约30%）。DAMGO延长了前I神经元爆发的吸气前阶段，而缺氧引起吸气后（48%）或吸气（22%）活动的转变，并使30%的细胞沉默。前-I神经元的反应与其rostrocaudal位置或形态不相关。DAMGO和缺氧都不改变膜电位I型神经元，但分别降低了33%和21%的输入电阻。相反的DAMGO-和缺氧诱发的相移前-I神经元的活动，反映了相应的前/后吸气驱动电位在I型神经元的变化，部分，由电压敏感染料成像的延髓神经元群体的活动。研究结果表明，阿片类药物在突触前延迟I型神经元的激活，将其作为从pFRG驱动到preBotC的目标。相反，缺氧似乎部分同步pFRG和preBotC节律发生器。这可能增强吸气和吸气后延髓活动，以触发多次吸气运动爆发。
Differential responses to opioids established the hypothesis that pre/postinspiratory (Pre-I) neurons of the parafacial respiratory group (pFRG) and inspiratory (Insp) neurons of the pre-Botzinger complex (preBotC) constitute a dual brainstem respiratory center. For further analysis of pFRG/preBotC interactions, we studied in newborn rat brainstem-spinal cord preparations opioid and anoxia effects on histologically identified pFRG-driven "type-I" Insp preBotC neurons and Pre-I neurons from three distinct respiratory brainstem regions. The mu-opioid [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) slowed inspiratory-related cervical nerve bursts quantally, whereas anoxia induced nonquantal slowing and repetitive cervical bursts. DAMGO had no effect on membrane potential or input resistance of Pre-I neurons, while anoxia hyperpolarized them (similar to 5 mV) and decreased their resistance (similar to 30%). DAMGO prolonged the preinspiratory phase of Pre-I neuron bursting, whereas anoxia caused a shift to post-inspiratory (48%) or inspiratory (22%) activity and silenced further 30% of cells. Pre-I neuron responses were not correlated with their rostrocaudal location or morphology. Neither DAMGO nor anoxia changed membrane potential type-I neurons, but decreased their input resistance by 33% and 21%, respectively. The opposite DAMGO- and anoxia-evoked phase shifts of Pre-I neuron activity were reflected by corresponding shifts of pre/postinspiratory drive potentials in type-I neurons and, partly, by voltage-sensitive dye-imaged medullary neuronal population activities. The findings suggest that opioids presynaptically delay activation of type-I neurons as the target of drive from the pFRG to the preBotC. Contrary, anoxia seems to partly synchronize the pFRG and preBotC rhythm generators. This may enhance inspiratory and postinspiratory medullary activities for triggering multiple inspiratory motor bursts.