Matosevich Noa, Regev Noa, Kimchy Uddi, Zelinger Noam, Kabaha Sina, Gabay Noam, Marmelshtein Amit, Nir Yuval
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Department of Physiology and Pharmacology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Sci Adv. 2025 Sep 12;11(37):eadw6375. doi: 10.1126/sciadv.adw6375. Epub 2025 Sep 10.
The locus coeruleus-norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the and circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-channelrhodopsin (ChR2) activation or Platynereis dumerilii ciliary opsin (PdCO) silencing of synapses in target regions, revealed a role for early activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.
蓝斑 - 去甲肾上腺素（LC - NE）系统调节觉醒；然而，尚不清楚蓝斑是以全局方式还是以特定环路方式发挥此作用。我们假设感觉诱发的觉醒主要由特定的LC - NE传出通路调节。对涉及小鼠基底前脑（BF）和脑桥网状核（PRN）的LC - NE通路的解剖学、生理学和功能模块性进行了测试。我们发现了 和 环路之间的部分解剖学分离。BF和PRN中的细胞外去甲肾上腺素动力学在睡眠期间表现出不同的声音诱发激活，包括PRN特有的快速声音诱发去甲肾上腺素峰值。通过逆行通道视紫红质（ChR2）激活或靶区域突触的多毛类动物纤毛视蛋白（PdCO）沉默对LC传出通路进行因果光遗传学研究，揭示了早期 活动在驱动觉醒和声音诱发觉醒中的作用。总之，我们的结果揭示了早期LC - NE 活动在连接感觉和觉醒通路中的作用，并确立了LC在调节觉醒方面的异质性。
