Stress Regulation of Sustained Attention and the Cholinergic Attention System
Stress Regulation of Sustained Attention and the Cholinergic Attention System
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DOI：
10.1016/j.biopsych.2020.04.013
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发表时间：
2020-10-01
影响因子：
10.6
通讯作者：
Bangasser, Debra A.
中科院分区：
文献类型：
--
作者：
Eck, Samantha R.;Xu, Song-Jun;Bangasser, Debra A.
背景技术背景：压力会加剧精神分裂症和注意力缺陷/多动症的症状，其特征是持续注意力受损。然而，压力如何调节注意力在很大程度上仍未被探索。我们研究了持续6天的可变应激是否改变了雄性和雌性大鼠的持续注意和胆碱能注意系统。维持注意任务的成功完成依赖于Meynert基底核（NBM）胆碱能神经元向皮层释放乙酰胆碱（ACh）。因此，我们评估是否可变应力（VS）改变了这些神经元的形态与一种新的方法，使用Cre依赖性病毒在基因修饰的ChAT：：Cre大鼠，一个物种用于这种操作。接下来，电化学记录测量皮质ACh VS。最后，我们用RNA测序来确定VS诱导的转录变化在NBM。结果：VS受损的注意力表现在持续的注意力任务，增加了树突的复杂性NBM胆碱能神经元在两种性别。NBM胆碱能神经元主要受抑制控制，因此这种形态学变化可以增加对这些神经元的抑制，减少下游ACh释放，从而损害注意力。事实上，VS减少了雄性大鼠前额叶皮层中ACh的释放。全球转录变化的定量显示，虽然VS诱导许多性别特异性的基因表达的变化，它增加了几个信号分子在both sexuals.CONCLUSIONS：这些研究表明，VS通过诱导NBM的分子和形态学变化损害注意力。确定压力调节注意力的机制可能会指导注意力缺陷精神疾病的新型治疗方法的开发。
BACKGROUND: Stress exacerbates symptoms of schizophrenia and attention-deficit/hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. We investigated whether a 6-day variable stressor altered sustained attention and the cholinergic attention system in male and female rats.METHODS: Sustained attention was tested with the sustained attention task. Successful performance on the sus-tained attention task relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nu-cleus basalis of Meynert (NBM). Thus, we evaluated whether variable stress (VS) altered the morphology of these neurons with a novel approach using a Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNA sequencing to identify VS-induced transcriptional changes in the NBM.RESULTS: VS impaired attentional performance in the sustained attention task and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of male rats. Quantification of global tran-scriptional changes revealed that although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes.CONCLUSIONS: These studies suggest that VS impairs attention by inducing molecular and morphological changes in the NBM. Identifying mechanisms by which stress regulates attention may guide the development of novel treatments for psychiatric disorders with attention deficits.