Xu Xiang-Ying, Xiao Yue, Liu Xu, Huang Yue, Ji Ying, Ji Yawei, Gao Yuan, Liu Su, Yang Jian-Jun, Cao Jun-Li, Zhou Chunyi, Xiao Cheng
Jiangsu Province Key Laboratory of Anesthesiology, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Nat Commun. 2025 May 16;16(1):4560. doi: 10.1038/s41467-025-59857-1.
Much progress has been made in the understanding of the neural circuits associated with sleep and anesthesia. As an important component among these circuits, the forebrain nuclei have been frequently interrogated. This study demonstrates that glutamatergic (Glu) neurons in the ventral pallidum (VP) enhance activity upon salient stimuli and state-dependently modulate brain arousal and motor activity in freely behaving male mice, and bidirectionally regulate the induction of and emergence from isoflurane general anesthesia. We delineate a neural pathway, consisting of VP Glu neurons→ noradrenergic (NA) neurons in the locus coeruleus (LC)→the lateral hypothalamus (LH) in male mice, controlling the release of noradrenaline in the LH and state-dependently modulated brain arousal, motor activity, and isoflurane general anesthesia through α2a receptors in the LH. Therefore, the VP-LC-LH pathway and α2a receptors in the LH may be promising state-dependent regulators of brain arousal in both freely behaving and anesthetized states.
在理解与睡眠和麻醉相关的神经回路方面已经取得了很大进展。作为这些回路中的一个重要组成部分，前脑核经常受到研究。这项研究表明，腹侧苍白球（VP）中的谷氨酸能（Glu）神经元在显著刺激下会增强活动，并根据状态调节自由活动雄性小鼠的大脑觉醒和运动活动，并且双向调节异氟烷全身麻醉的诱导和苏醒。我们描绘了一条神经通路，在雄性小鼠中由VP Glu神经元→蓝斑（LC）中的去甲肾上腺素能（NA）神经元→下丘脑外侧区（LH）组成，通过LH中的α2a受体控制LH中去甲肾上腺素的释放，并根据状态调节大脑觉醒、运动活动和异氟烷全身麻醉。因此，VP-LC-LH通路和LH中的α2a受体可能是在自由活动和麻醉状态下有前景的大脑觉醒状态依赖性调节因子。
