The locus coeruleus (LC) is a critical node in the stress response, and its activation has been shown to promote hypervigilance and anxiety-like behavior. This noradrenergic nucleus has historically been considered homogeneous with highly divergent neurons that operate en masse to collectively affect central nervous system function and behavioral state. However, in recent years, LC has been identified as a heterogeneous structure whose neurons innervate discrete terminal fields and contribute to distinct aspects of behavior. We have previously shown that in late adolescent male rats, an acute traumatic stressor, simultaneous physical restraint and exposure to predator odor, preferentially induces c-Fos expression in a subset of dorsal LC neurons and persistently increases anxiety-like behavior. To investigate how these neurons respond to and contribute to the behavioral response to stress, we used a combination of retrograde tracing, whole-cell patch clamp electrophysiology, and chemogenetics. Here we show that LC neurons innervating the central nucleus of the amygdala (CeA) and medial prefrontal cortex (mPFC) undergo distinct electrophysiological changes in response to stressor exposure and have opposing roles in mediating anxiety-like behavior. While neurons innervating CeA become more excitable in response to stress and promote anxiety-like behavior, those innervating mPFC become less excitable and appear to promote exploration. These findings show that LC neurons innervating distinct terminal fields have unique physiological responses to particular stimuli. Furthermore, these observations advance the understanding of the LC as a complex and heterogeneous structure whose neurons maintain unique roles in various forms of behavior.

蓝斑 (LC) 是应激反应中的一个关键节点，其激活已被证明会促进过度警觉和焦虑样行为。这种去甲肾上腺素能核在历史上被认为是同质的，具有高度发散的神经元，这些神经元聚集在一起，共同影响中枢神经系统的功能和行为状态。然而，近年来，LC 已被确定为一种异质结构，其神经元支配离散的终端场并有助于行为的不同方面。我们之前已经表明，在青春期晚期的雄性大鼠中，一种急性创伤性压力源，同时身体约束和暴露于捕食者气味，优先诱导背侧 LC 神经元子集的 c-Fos 表达，并持续增加焦虑样行为。为了研究这些神经元如何响应并促成对压力的行为反应，我们结合了逆行追踪、全细胞膜片钳电生理学和化学遗传学。在这里，我们显示支配杏仁核中央核 (CeA) 和内侧前额叶皮层 (mPFC) 的 LC 神经元在响应压力源暴露时经历不同的电生理变化，并且在介导焦虑样行为中具有相反的作用。虽然支配 CeA 的神经元对压力的反应变得更加兴奋并促进类似焦虑的行为，但支配 mPFC 的那些神经元变得不那么兴奋并且似乎促进探索。这些发现表明，支配不同末端场的 LC 神经元对特定刺激具有独特的生理反应。此外，