Identification and characterization of a sleep-active cell group in the rostral medullary brainstem.
Identification and characterization of a sleep-active cell group in the rostral medullary brainstem.
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DOI：
10.1523/jneurosci.0620-12.2012
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发表时间：
2012-12-12
期刊：
影响因子：
--
通讯作者：
Lu J
中科院分区：
文献类型：
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作者：
Anaclet C;Lin JS;Vetrivelan R;Krenzer M;Vong L;Fuller PM;Lu J
早期的横断和刺激研究表明，髓质脑干中存在促进睡眠的回路，但构成这种假定的催眠回路的神经元的位置和身份仍然悬而未决。在本研究中，我们试图揭示可能有助于睡眠调节的髓质神经元的位置和身份。在这里，我们在大鼠中显示：1）位于面神经外侧和背侧的髓质神经元的界定节点 - 我们称为面旁区（PZ）的区域 - 投射到促进唤醒的内侧臂旁核（MPB）； 2) PZ神经元在睡眠后表达c-Fos，但在清醒后不表达，因此是睡眠活跃的； 3) PZ 的细胞体特异性损伤导致每日清醒度大幅持续增加 (50%)，但以慢波睡眠 (SWS) 为代价。使用转基因报告小鼠 (VGAT-GFP)，我们发现 >50% 的 PZ 睡眠活跃神经元本质上是抑制性的（GABA 能/甘氨酸能，VGAT+）。最后，我们使用表达 Cre 的腺相关病毒 (AAV) 载体和条件性 Vgatlox/lox 小鼠来选择性地从基因上破坏 PZ 神经元的 GABA/甘氨酸能神经传递。 PZ GABA 能/甘氨酸能神经传递的破坏导致每日清醒度持续增加 (40%)，但牺牲了 SWS 和 REM 睡眠。这些结果综合起来揭示了延髓脑干头端睡眠活跃神经元界定节点的位置和神经化学特性。
Early transection and stimulation studies suggested the existence of sleep-promoting circuitry in the medullary brainstem, yet the location and identity of the neurons comprising this putative hypnogenic circuitry remains unresolved. In the present study, we sought to uncover the location and identity of medullary neurons that might contribute to the regulation of sleep. Here we show in rats that 1) a delimited node of medullary neurons located lateral and dorsal to the facial nerve – a region we termed the parafacial zone (PZ) - project to the wake-promoting medial parabrachial nucleus (MPB); 2) PZ neurons express c-Fos after sleep but not after wakefulness and hence are sleep-active; and 3) cell-body specific lesions of the PZ result in large and sustained increases (50%) in daily wakefulness at the expense of slow-wave-sleep (SWS). Using transgenic reporter mice (VGAT-GFP) we then show that >50% of PZ sleep-active neurons are inhibitory (GABAergic/glycinergic, VGAT+) in nature. Finally, we used a Cre-expressing adeno-associated viral (AAV) vector and conditional Vgatlox/lox mice to selectively and genetically disrupt GABA/glycinergic neurotransmission from PZ neurons. Disruption of PZ GABAergic/glycinergic neurotransmission resulted in sustained increases (40%) in daily wakefulness at the expense of both SWS and REM sleep. These results taken together reveal the location and neurochemical identity of a delimited node of sleep-active neurons within the rostral medullary brainstem.