Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice
Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice
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网状丘脑去甲肾上腺素能末端的激活延迟了小鼠异丙酚麻醉的唤醒
DOI：
10.1096/fj.201802164rr
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发表时间：
2019-06-01
期刊：
影响因子：
4.8
通讯作者：
Yu, Tian
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Fu, Bao;Yu, Tian
异丙酚（PRO）麻醉期间的脑电图监测通常表现为低频振荡，这可能与丘脑网状核（TRN）调节有关。TRN接受蓝斑（LC）的去肾上腺素能输入。我们假设TRN中特定的去肾上腺素能连接可能有助于PRO麻醉的出现。采用核内去甲肾上腺素（NE）注射（n = 10）和设计药物特异性激活的设计受体（DREADDs） （n = 10）来研究PRO麻醉期间LC到TRN的去甲肾上腺素能输入的作用。利用急性脑切片制备中的全细胞记录来鉴定调节TRN中去甲肾上腺素能神经支配的肾上腺素能受体类型。脑内注射NE到TRN会延迟PRO麻醉恢复小鼠的觉醒（平均+/- sd； NE注射组486.6 +/- 57.32 s，对照组422.4 +/- 48.19 s, P = 0.0143），并增加皮质δ振荡（0.1-4 Hz， NE注射组25.4 +/- 2.9 s，对照组21.0 +/- 1.7 s, P = 0.0094）。trn内注射NE也降低了pro致昏迷的EC50（注射组为57.05 +/- 1.78 mg/kg，对照组为72.44 +/- 3.23 mg/kg, P = 0.0096）。此外，使用DREADDs激活TRN的lc -去甲肾上腺素能神经末梢增加了恢复时间[氯氮平n -氧化（CNO）注射组为466.1 +/- 44.57 s，对照组为426.1 +/- 38.75 s；P = 0.0033]，降低了PRO致昏迷的EC50 (CNO注射组为64.77 +/- 3.40 mg/kg，对照组为74.00 +/- 2.08 mg/kg, P = 0.0081)，增加了PRO麻醉时皮质δ振荡（CNO注射组为23.29 +/- 2.58，对照组为19.56 +/- 1.9,P = 0.0213）。此外，全细胞记录显示，NE通过α 1-肾上腺素受体增强了TRN神经元的抑制性突触后电流。我们的数据表明，在LC-TRN投射的去甲肾上腺素能末端，NE信号的增强延迟了全身麻醉的唤醒，这可能是由α - 1肾上腺素能受体激活介导的。我们的发现为进一步了解各种LC靶点在麻醉和觉醒中的功能打开了一扇门。-张勇，付斌，刘春春，于生，罗婷，张磊，周伟，于涛，网状丘脑去甲肾上腺素能末端的激活延迟异丙酚麻醉小鼠的觉醒。
Electroencephalogram monitoring during propofol (PRO) anesthesia typically features low-frequency oscillations, which may be involved with thalamic reticular nucleus (TRN) modulation. TRN receives noradrenergic inputs from the locus coeruleus (LC). We hypothesized that specific noradrenergic connections in the TRN may contribute to the emergence from PRO anesthesia. Intranuclei norepinephrine (NE) injections (n = 10) and designer receptors exclusively activated by designer drugs (DREADDs) (n = 10) were used to investigate the role of noradrenergic inputs from the LC to the TRN during PRO anesthesia. Whole-cell recording in acute brain slice preparations was used to identify the type of adrenoceptor that regulates noradrenergic innervation in the TRN. An intracerebral injection of NE into the TRN delays arousal in mice recovering from PRO anesthesia (means +/- sd; 486.6 +/- 57.32 s for the NE injection group vs. 422.4 +/- 48.19 s for the control group; P = 0.0143) and increases the cortical-delta (0.1-4 Hz, 25.4 +/- 2.9 for the NE injection group vs. 21.0 +/- 1.7 for the control group; P = 0.0094) oscillation. An intra-TRN injection of NE also decreased the EC50 of PRO-induced unconsciousness (57.05 +/- 1.78 mg/kg for the NE injection group vs. 72.44 +/- 3.23 mg/kg for the control group; P = 0.0096). Moreover, the activation of LC-noradrenergic nerve terminals in the TRN using DREADDs increased the recovery time [466.1 +/- 44.57 s for the clozapine N-oxide (CNO) injection group vs. 426.1 +/- 38.75 s for the control group; P = 0.0033], decreased the EC50 of PRO-induced unconsciousness (64.77 +/- 3.40 mg/kg for the CNO injection group vs. 74.00 +/- 2.08 mg/kg for the control group; P = 0.0081), and increased the cortical-delta oscillation during PRO anesthesia (23.29 +/- 2.58 for the CNO injection group vs. 19.56 +/- 1.9 for the control group; P = 0.0213). In addition, whole-cell recording revealed that NE augmented the inhibitory postsynaptic currents in the TRN neurons via the alpha 1-adrenoceptor. Our data indicated that enhanced NE signaling at the noradrenergic terminals of the LC-TRN projection delays arousal from general anesthesia, which is likely mediated by the alpha 1-adrenoceptor activation. Our findings open a door for further understanding of the functions of various LC targets in both anesthesia and arousal.-Zhang, Y., Fu, B., Liu, C., Yu, S., Luo, T., Zhang, L., Zhou, W., Yu, T. Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice.