近日，浙江大学教授汪浩及其研究组提出了谷氨酸能中脑导水管周围灰质对共规则位点的投射在威胁情境中协调适应性唤醒状态。相关论文于2025年8月25日发表在《神经科学通报》杂志上。

该研究团队发现小鼠腹外侧导水管周围灰质（vlPAG）向LC的谷氨酸能投射是芳香动力学的关键调节因子。纤维光度记录揭示了应力诱导的vlPAG^CaMKIIα-LC轴索末端在不同威胁范式下的Ca²⁺动态。切片电生理表明，该通路通过谷氨酸能传递介导LC-去甲肾上腺素（LC-NE）神经元活动。低频通路激活（1hz）主要诱导焦虑样行为，而高频刺激（10hz）诱发更多的恐慌样过度运动，建立了频率依赖的芳香状态连续体。相反，途径抑制降低了瞳孔大小（一个可靠的芳香生物标志物），同时抑制了威胁回避行为和缓解焦虑相关行为，而不改变环境偏好。这些发现表明，vlPAG^CaMKIIα-LC通路维持基线芳香性，同时动态调节威胁诱导的高芳香性。

据了解，蓝斑（LC）作为通过紧张性活动调控觉醒状态的去甲肾上腺素核团，需要精确的调节机制来维持其动态激活水平。然而，LC活动维持背后的神经回路仍不清楚。

附：英文原文

Title: Glutamatergic Periaqueductal Gray Projections to the Locus Coeruleus Orchestrate Adaptive Arousal States in Threatening Contexts

Author: Wang, Siyu, Yang, Yiwen, Hao, Sijia, Sun, Yanhui, Wang, Hao

Issue&Volume: 2025-08-25

Abstract: The locus coeruleus (LC), a norepinephrine nucleus governing arousal states through tonic activity, requires precise regulatory mechanisms to maintain its dynamic activation levels. However, the neural circuitry underlying LC activity maintenance remains unclear. Here, we identify a glutamatergic projection from the ventrolateral periaqueductal gray (vlPAG) to the LC in mice as a critical regulator of arousal dynamics. Fiber photometry recordings revealed stress-induced Ca2+ dynamics in vlPAGCaMKIIα-LC axon terminals across diverse threat paradigms. Slice electrophysiology demonstrated that this pathway mediates LC-norepinephrine (LC-NE) neuronal activity via glutamatergic transmission. Low-frequency pathway activation (1 Hz) mainly induced anxiety-like behaviors, whereas high-frequency stimulation (10 Hz) evoked more panic-like hyperlocomotion, establishing a frequency-dependent continuum of arousal states. Conversely, pathway inhibition reduced pupil size, a reliable biomarker for arousal, concurrently suppressing threat avoidance behaviors and alleviating anxiety-related behaviors without altering environmental preference. These findings reveal that the vlPAGCaMKIIα-LC pathway maintains baseline arousal while dynamically scaling threat-induced hyperarousal.

DOI: 10.1007/s12264-025-01491-4

Source: https://link.springer.com/article/10.1007/s12264-025-01491-4