Graduate School of Biomedical Sciences, Rowan University, 42 East Laurel Road, Stratford, NJ 08084, USA.
Graduate School of Biomedical Sciences, Rowan University, 42 East Laurel Road, Stratford, NJ 08084, USA; Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, 2 Medical Center Drive, Stratford, NJ 08084, USA.
Neuroscience. 2018 Mar 1;373:7-19. doi: 10.1016/j.neuroscience.2018.01.020. Epub 2018 Jan 16.
Stress is a physiological state characterized by altered neuroendocrine signaling, behavioral arousal, and anxiety. Chronic or traumatic stress may predispose individuals for multiple somatic and psychiatric illnesses. The locus coeruleus (LC) is a major node in the stress response that integrates input from multiple stress responsive neural circuits and releases norepinephrine (NE) throughout the central nervous system (CNS) to promote vigilance and anxiety. Many mood disorders associated with prior stress are characterized by chronically altered noradrenergic signaling, yet the long-term impact of an acute stressor on LC function is not clear. To determine how acute stress could affect anxiety-like behavior as well as LC function at immediate and extended time points, rats underwent simultaneous exposure to physical restraint and predator odor. Rats underwent behavioral testing immediately or one week after stressor exposure and were then sacrificed for whole-cell patch-clamp recordings of LC neurons. Stress caused an immediate increase in anxiety-like behaviors in the elevated plus maze (EPM), as well decreased excitatory synaptic transmission and increased spontaneous discharge in LC neurons. These effects persisted for seven days after stress. Importantly, the excitability of LC neurons was increased one week post-stress, but not immediately after, suggesting a long-term adaptation by the system. Rats tested in the open field one week after stress also showed increased anxiety-like behaviors. These findings show that a single acute stressor is capable of precipitating long-lasting changes in the LC function that may be related to some of the behavioral effects of stress, potentially contributing to stress-induced disease pathogenesis.
压力是一种生理状态，其特征为神经内分泌信号改变、行为觉醒和焦虑。慢性或创伤性压力可能使个体易患多种躯体和精神疾病。蓝斑（LC）是应激反应的主要节点，它整合来自多个应激反应神经回路的输入，并在整个中枢神经系统（CNS）释放去甲肾上腺素（NE），以促进警觉和焦虑。许多与先前压力相关的情绪障碍的特征是去甲肾上腺素能信号的慢性改变，但急性应激源对 LC 功能的长期影响尚不清楚。为了确定急性应激如何影响焦虑样行为以及 LC 功能的即刻和扩展时间点，大鼠同时接受身体束缚和捕食者气味的暴露。大鼠在应激暴露后立即或一周后进行行为测试，然后进行 LC 神经元全细胞膜片钳记录。应激导致高架十字迷宫（EPM）中的焦虑样行为立即增加，同时减少 LC 神经元的兴奋性突触传递并增加自发性放电。这些影响在应激后持续七天。重要的是，LC 神经元的兴奋性在应激后一周增加，但不在应激后立即增加，这表明系统发生了长期适应。应激后一周在开阔场中测试的大鼠也表现出焦虑样行为增加。这些发现表明，单次急性应激源能够引发 LC 功能的持久变化，这可能与应激的一些行为效应有关，从而可能导致应激诱导的疾病发病机制。
