Activation of orexin-2 receptors in the Kӧlliker-Fuse nucleus of anesthetized mice leads to transient slowing of respiratory rate.

Activation of orexin-2 receptors in the Kӧlliker-Fuse nucleus of anesthetized mice leads to transient slowing of respiratory rate.
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DOI:
10.3389/fphys.2022.977569
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发表时间:
2022
影响因子:
4
通讯作者:
Levitt, Erica S. S.
Levitt, Erica S. S.
中科院分区:
医学2区
文献类型:
--
作者:
Varga, Adrienn G. G.;Whitaker-Fornek, Jessica R. R.;Maletz, Sebastian N. N.;Levitt, Erica S. S.

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食欲素是源自下丘脑的神经肽,具有广泛的生理作用,包括调节自主功能、睡眠-觉醒状态、觉醒和呼吸。缺乏食欲素可能会导致发作性睡病和睡眠呼吸障碍。食欲素能下丘脑神经元将纤维发送到直接投射到前腹侧呼吸群、膈和舌下运动神经元的 Kølliker-Fuse (KF) 神经元。这些联系表明食欲素调节的 KF 神经元在功能上连接觉醒/唤醒和呼吸的控制中的潜在作用。在幼年大鼠的减量制剂中,将 Orexin B 显微注射到 KF 中,导致呼吸频率和舌下输出短暂增加,但尚未探索完整制剂中 Orexin B 对 KF 的调节。在这里,我们在自主呼吸、异氟醚麻醉的野生型小鼠的 KF 中显微注射了 Orexin B 小鼠肽和合成的 Orexin 2 受体激动剂 MDK 5220。将 Orexin-2 受体激动剂微量注射到 KF 中会导致呼吸频率短暂减慢,与注射 MDK 5220 相比,对 Orexin-B 的反应更为夸张。我们的数据表明 KF 中的 Orexin B 信号传导可能有助于唤醒介导的呼吸反应。
Orexins are neuropeptides originating from the hypothalamus that serve broad physiological roles, including the regulation of autonomic function, sleep-wake states, arousal and breathing. Lack of orexins may lead to narcolepsy and sleep disordered breathing. Orexinergic hypothalamic neurons send fibers to Kӧlliker-Fuse (KF) neurons that directly project to the rostroventral respiratory group, and phrenic and hypoglossal motor neurons. These connections indicate a potential role of orexin-modulated KF neurons in functionally linking the control of wakefulness/arousal and respiration. In a reduced preparation of juvenile rats Orexin B microinjected into the KF led to a transient increase in respiratory rate and hypoglossal output, however Orexin B modulation of the KF in intact preparations has not been explored. Here, we performed microinjections of the Orexin B mouse peptide and the synthetic Orexin 2 receptor agonist, MDK 5220, in the KF of spontaneously breathing, isoflurane anesthetized wild type mice. Microinjection of Orexin-2 receptor agonists into the KF led to transient slowing of respiratory rate, which was more exaggerated in response to Orexin-B than MDK 5220 injections. Our data suggest that Orexin B signaling in the KF may contribute to arousal-mediated respiratory responses.
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