华盛顿大学Michael R. Bruchas研究组揭示了异质核周围神经元调节唤醒和探索行为。这一研究成果发表在2025年5月7日出版的国际学术期刊《自然》上。

在这里，研究组确定了一群在转录、空间和功能上多样化的GABAergic （γ-氨基丁酸产生）神经元，它们接受远端输入并调节LC放电模式，以控制全局芳香水平和芳香相关的加工和行为。小组定义了LC周围的解剖主题病毒追踪，并将单细胞RNA测序与空间转录组学相结合，从分子上定义LC去甲肾上腺素产生和LC周围细胞类型。课题组人员确定了几种神经元细胞类型，它们构成了LC周围功能多样性的基础，并在行为小鼠中采用了一系列互补的神经回路方法。他们的研究结果表明，LC和LC周围神经元在转录、功能和解剖学上都是异质的，它们是调节芳香和回避状态的神经元群体。定义LC和LC周围的分子、细胞和功能多样性为理解芳香性、动机性和神经精神疾病的神经生物学基础提供了路线图。

据悉，作为去甲肾上腺素在大脑中的主要来源，局部蓝蛋白（locthem coerulethem， LC）调节芳香、回避和应激反应。然而，局部神经调节输入如何控制LC功能仍未解决。

附：英文原文

Title: Heterogeneous pericoerulear neurons tune arousal and exploratory behaviours

Author: Luskin, Andrew T., Li, Li, Fu, Xiaonan, Martin, Madison M., Barcomb, Kelsey, Girven, Kasey S., Blackburn, Taylor, Wells, Bailey A., Thai, Sarah T., Li, Esther M., Rana, Akshay N., Simon, Rhiana C., Sun, Li, Gao, Lei, Murry, Alexandria D., Golden, Sam A., Stuber, Garret D., Ford, Christopher P., Gu, Liangcai, Bruchas, Michael R.

Issue&Volume: 2025-05-07

Abstract: As the primary source of noradrenaline in the brain, the locus coeruleus (LC) regulates arousal, avoidance and stress responses1,2. However, how local neuromodulatory inputs control LC function remains unresolved. Here we identify a population of transcriptionally, spatially and functionally diverse GABAergic (γ-aminobutyric acid-producing) neurons in the LC dendritic field that receive distant inputs and modulate modes of LC firing to control global arousal levels and arousal-related processing and behaviours. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing with spatial transcriptomics to molecularly define both LC noradrenaline-producing and peri-LC cell types. We identify several neuronal cell types that underlie peri-LC functional diversity using a series of complementary neural circuit approaches in behaving mice. Our findings indicate that LC and peri-LC neurons are transcriptionally, functionally and anatomically heterogenous neuronal populations that modulate arousal and avoidance states. Defining the molecular, cellular and functional diversity of the LC and peri-LC provides a roadmap for understanding the neurobiological basis of arousal, motivation and neuropsychiatric disorders.

DOI: 10.1038/s41586-025-08952-w

Source: https://www.nature.com/articles/s41586-025-08952-w