Neuroanatomical Basis for the Orexinergic Modulation of Anesthesia Arousal and Pain Control.
Neuroanatomical Basis for the Orexinergic Modulation of Anesthesia Arousal and Pain Control.
复制标题
DOI：
10.3389/fncel.2022.891631
复制
发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
下丘脑增食欲素（hypocretin）神经元在唤醒控制中起着至关重要的作用。它们在麻醉和镇痛中的作用还有待进一步了解。为了加深我们对神经解剖学的认识，我们用共聚焦显微镜和光片显微镜对增食欲素神经元的投射进行了系统的定位。我们通过腺相关病毒感染小鼠大脑，在食欲素神经元中特异性表达标记有荧光标记物的光遗传学视蛋白。成像结果揭示了整个大脑中食欲素投射的细节和新特征，特别是与调节唤醒和疼痛的核团有关。然后，我们光遗传学激活下丘脑外侧的食欲素神经元，以研究对麻醉相关行为的影响。cFos染色显示，ChR 2-mCherry组中的光遗传学刺激可激活食欲素神经元，而对照mCherry组则不能（62.86 ± 3.923%对7.9 ± 2.072%; P < 0.0001）。在行为测定中，ChR 2-mCherry组中的光遗传学刺激一致地引起轻度异氟烷麻醉的强烈唤醒（9.429 ± 3.804 s vs.238.2 ± 17.42 s; P < 0.0001），缩短异氟醚深麻醉后苏醒时间（109.5 ± 13.59 s vs.213.8 ± 21.77 s; P = 0.0023），并增加热板试验中的缩爪潜伏期（11.45 ± 1.185 s vs.8.767 ± 0.7775; P = 0.0317）。食欲素纤维的结构细节为研究食欲素在麻醉和镇痛中的作用奠定了神经解剖学基础。
Hypothalamic orexin (hypocretin) neurons play crucial roles in arousal control. Their involvement in anesthesia and analgesia remains to be better understood. In order to enhance our view on the neuroanatomy, we systematically mapped the projections of orexin neurons with confocal microscope and light sheet microscope. We specifically expressed optogenetic opsins tagged with fluorescence markers in orexin neurons through adeno-associated viral infection in the mouse brain. The imaging results revealed fine details and novel features of the orexin projections throughout the brain, particularly related to the nuclei regulating arousal and pain. We then optogenetically activated orexin neurons in the lateral hypothalamus to study the effects on anesthesia-related behaviors. cFos staining showed that optogenetic stimulation can activate orexin neurons in the ChR2-mCherry group, but not the control mCherry group (62.86 ± 3.923% vs. 7.9 ± 2.072%; P < 0.0001). In behavior assays, optogenetic stimulation in the ChR2-mCherry group consistently elicited robust arousal from light isoflurane anesthesia (9.429 ± 3.804 s vs. 238.2 ± 17.42 s; P < 0.0001), shortened the emergence time after deep isoflurane anesthesia (109.5 ± 13.59 s vs. 213.8 ± 21.77 s; P = 0.0023), and increased the paw withdrawal latency in a hotplate test (11.45 ± 1.185 s vs. 8.767 ± 0.7775; P = 0.0317). The structural details of orexin fibers established the neuroanatomic basis for studying the role of orexin in anesthesia and analgesia.
登录
查看更多内容
DOI：
10.1073/pnas.1202526109
发表时间：
2012-09-25
影响因子：
11.1
作者：
Carter, Matthew E.;Brill, Julia;de Lecea, Luis
通讯作者：
de Lecea, Luis
影响因子：
64.5
作者：
Lin, L;Faraco, J;Mignot, E
通讯作者：
Mignot, E
影响因子：
9.2
作者：
Liang, Yue;Shi, Wu;Zhang, Ling
通讯作者：
Zhang, Ling
影响因子：
2.5
作者：
Iyer, Manasi;Essner, Rachel A.;Carter, Matthew E.
通讯作者：
Carter, Matthew E.
影响因子：
9.9
作者：
Arnulf, I;Bonnet, AM;Agid, Y
通讯作者：
Agid, Y