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Excitation-Inhibition Imbalance Leads to Alteration of Neuronal Coherence and Neurovascular Coupling under Acute Stress
Journal of Neuroscience ( IF 4.4 ) Pub Date : 2020-11-18 , DOI: 10.1523/jneurosci.1553-20.2020
Kayoung Han , Myunghee Lee , Hyun-Kyoung Lim , Minwoo Wendy Jang , Jea Kwon , C. Justin Lee , Seong-Gi Kim , Minah Suh

A single stressful event can cause morphologic and functional changes in neurons and even malfunction of vascular systems, which can lead to acute stress disorder or post-traumatic stress disorder. However, there is a lack of evidence regarding how acute stress impacts neuronal activity, the concurrent vascular response, and the relationship between these two factors, which is defined as neurovascular coupling. Here, using in vivo two-photon imaging, we found that NMDA-evoked calcium transients of excitatory neurons were impaired and that vasodilation of penetrating arterioles was concomitantly disrupted in acutely stressed male mice. Furthermore, acute stress altered the relationship between excitatory neuronal calcium coherence and vascular responses. By measuring NMDA-evoked excitatory and inhibitory neuronal calcium activity in acute brain slices, we confirmed that neuronal coherence both between excitatory neurons and between excitatory and inhibitory neurons was reduced by acute stress but restored by blockade of glucocorticoid receptor signaling. Furthermore, the ratio of sEPSCs to sIPSCs was altered by acute stress, suggesting that the excitation-inhibition balance was disrupted by acute stress. In summary, in vivo, ex vivo, and whole-cell recording studies demonstrate that acute stress modifies excitatory-inhibitory neuronal coherence, disrupts the excitation-inhibition balance, and causes consequent neurovascular coupling changes, providing critical insights into the neural mechanism of stress-induced disorders.

SIGNIFICANCE STATEMENT Acute stress can cause pathologic conditions, such as acute stress disorder and post-traumatic stress disorder, by affecting the functions of neurons and blood vessels. However, investigations into the impacts of acute stress on neurovascular coupling, the tight connection between local neural activity and subsequent blood flow changes, are lacking. Through investigations at the in vivo, ex vivo, and whole-cell recording levels, we found that acute stress alters the NMDA-evoked vascular response, impairs the function and coherence of excitatory and inhibitory neurons, and disrupts the excitatory and inhibitory balance. These novel findings provide insights into the relevance of the excitatory-inhibitory balance, neuronal coherence, and neurovascular coupling to stress-induced disorders.



中文翻译:

兴奋抑制失衡导致急性应激下神经元连贯性和神经血管耦合的改变。

单个应激事件可能会导致神经元的形态和功能变化,甚至导致血管系统功能异常,从而可能导致急性应激障碍或创伤后应激障碍。但是,关于急性应激如何影响神经元活动,同时发生的血管反应以及这两个因素之间的关系(这被定义为神经血管耦合),缺乏证据。在这里,使用体内在双光子成像中,我们发现在急性应激的雄性小鼠中,NMDA引起的兴奋性神经元钙瞬变受到损害,并且穿透性小动脉的血管舒张同时受到破坏。此外,急性应激改变了兴奋性神经元钙的凝聚力与血管反应之间的关系。通过测量急性脑切片中NMDA诱发的兴奋性和抑制性神经元钙的活性,我们证实了急性应激可降低兴奋性神经元之间以及兴奋性和抑制性神经元之间的神经元相干性,但可通过糖皮质激素受体信号传导的阻断来恢复。此外,急性应激改变了sEPSC与sIPSC的比例,表明激发抑制平衡被急性应激所破坏。总之,在体内离体和全细胞记录研究表明,急性应激会改变兴奋性抑制性神经元的连贯性,破坏兴奋性抑制性平衡,并导致随之而来的神经血管耦合变化,从而为应激性疾病的神经机制提供重要见解。

重要声明急性应激可通过影响神经元和血管的功能而引起病理状况,例如急性应激障碍和创伤后应激障碍。但是,缺乏对急性应激对神经血管耦合,局部神经活动与随后的血流变化之间紧密联系的影响的研究。通过体内体外研究以及全细胞记录水平,我们发现急性应激会改变NMDA诱发的血管反应,损害兴奋性和抑制性神经元的功能和连贯性,并破坏兴奋性和抑制性平衡。这些新颖的发现提供了对兴奋性抑制平衡,神经元连贯性和神经血管耦合与应激性疾病的相关性的见解。

更新日期:2020-11-19
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