Molecular control of locus coeruleus neurotransmission
Molecular control of locus coeruleus neurotransmission
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DOI：
10.1016/s0006-3223(99)00158-4
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发表时间：
1999-11-01
影响因子：
10.6
通讯作者：
Aghajanian, GK
中科院分区：
文献类型：
--
作者：
Nestler, EJ;Alreja, M;Aghajanian, GK
蓝斑 (LC) 是大脑中主要的去甲肾上腺素能核，支配大部分神经轴。 LC 神经元被认为可以调节注意力和警觉状态以及交感神经系统的活动。这些神经元还与压力、抗抑郁药和阿片类药物对大脑的作用有关。部分得益于液晶相对均质的事实，我们可以了解一些控制其功能状态的细胞和分子机制。本综述重点关注 cAMP 通路在 LC 神经元调节中的作用，特别是在慢性扰动后。因此，在慢性应激或长期阿片类药物治疗后，LC 中该细胞内信号传导途径的几个成分上调，但在长期抗抑郁治疗后下调。 LC 神经元表现出起搏器活性，这似乎至少部分是由蛋白激酶 A 激活的非特异性阳离子电流介导的。因此，长期给药（例如压力或阿片类药物）后上调 cAMP 通路的刺激会增加 LC 神经元的兴奋性，而下调 cAMP 通路的刺激（例如抗抑郁药）会产生相反的效果。 影响。这种分子适应可能有助于与这些不同条件相关的行为可塑性。 (C) 1999 年生物精神病学协会。
The locus coeruleus (LC) is the major noradrenergic nucleus in the brain and innervates large segments of the neuraxis. LC neurons are thought to regulate states of attention and vigilance as well as activity of the sympathetic nervous system. These neurons also have been implicated in the actions of stress, antidepressants, and opiates on the brain. Aided in part by the fact that the LC is relatively homogeneous, it has been possible to understand some of the cellular and molecular mechanisms that control their functional state. This review focuses on the role played by the cAMP pathway in regulation of LC neurons, particularly after chronic perturbations. Thus, several components of this intracellular signaling pathway are upregulated in the LC after chronic stress or chronic opiate treatment, but downregulated after chronic antidepressant treatment. LC neurons exhibit a pacemaker activity, which appears to be mediated, at least in part, by a nonspecific cation current that is activated by protein kinase A. As a result, stimuli that upregulate the cAMP pathway after chronic administration (e.g., stress or opiates) increase the excitability of LC neurons, whereas stimuli that downregulate the cAMP pathway (e.g., antidepressants) exert the opposite effect. Such molecular adaptations could contribute to the behavioral plasticity that is associated with these various conditions. (C) 1999 Society of Biological Psychiatry.