CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.
CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.
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DOI：
10.1016/j.neuron.2015.07.002
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发表时间：
2015-08-05
期刊：
影响因子：
16.2
通讯作者：
Bruchas MR
中科院分区：
文献类型：
--
作者：
McCall JG;Al-Hasani R;Siuda ER;Hong DY;Norris AJ;Ford CP;Bruchas MR
蓝斑去甲肾上腺素能 (LC-NE) 系统是应激事件后最先启动的系统之一。虽然许多研究小组已经证明 LC-NE 神经元会被许多不同的压力源激活，但潜在的神经回路以及这种活动在产生压力引起的焦虑中的作用尚未阐明。结合体内化学遗传学、光遗传学和逆行追踪，我们确定 LC-NE 系统的强直活性增加对于压力引起的焦虑和厌恶是必要且充分的。在应激过程中选择性抑制 LC-NE 神经元可以防止随后的焦虑样行为。仅外源增加 LC-NE 神经元的强直性而非阶段性活动就足以产生焦虑样和厌恶行为。此外，来自杏仁核的内源性促肾上腺皮质激素释放激素+ (CRH+) LC 输入会增加强直 LC 活性，诱发焦虑样行为。这些研究将 LC-NE 系统定位为急性应激性焦虑的关键调节因子，并为预防应激相关的情感障碍提供了潜在的干预措施。
The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders.