Anesthesia differentially modulates neuronal and vascular contributions to the BOLD signal
Anesthesia differentially modulates neuronal and vascular contributions to the BOLD signal
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DOI：
10.1016/j.neuroimage.2019.03.057
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发表时间：
2019-07
期刊：
影响因子：
5.7
通讯作者：
Timo Mauritz van Alst;L. Wachsmuth;M. Datunashvili;Franziska Albers;N. Just;T. Budde;C. Faber
中科院分区：
文献类型：
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作者：
Timo Mauritz van Alst;L. Wachsmuth;M. Datunashvili;Franziska Albers;N. Just;T. Budde;C. Faber
在基础神经科学研究中，大多数涉及BOLD功能磁共振成像的研究都是在麻醉动物身上进行的。本研究通过BOLD功能磁共振成像，光学钙记录和ASL在体内的实验相结合，探讨神经和血液动力学活动。采用膜片钳技术观察离体神经元的电生理活动。研究了在恒定刺激下不同浓度异氟烷（ISO）和不同程度高碳酸血症诱发的多种麻醉深度的各种麻醉条件。我们观察到，不同的麻醉条件下获得的结果有重大影响，特别是麻醉可能会导致不同的实验modality.In通气的动物，强大的BOLD反应检测，即使在相对较深的麻醉，而在非通气的动物，BOLD反应在这些条件下是检测不到的。这很可能是由于呼吸抑制引起的高碳酸血症，因为在通气动物中给予CO2具有相同的效果。这一观察结果与灌注测量结果一致，表明吸入CO2显著增加灌注，而ISO则没有。在光学钙测量中，较高浓度的ISO降低自发神经活动，但不降低刺激诱发反应。这一观察结果被解释为ISO下神经元的兴奋性普遍较低，这抑制了自发活动，因此留下了更多的神经元可用于响应刺激而同步放电。将这种现象解释为独立的单个神经元的集成信号得到了膜片钳实验的支持，因为每个刺激的动作电位（AP）的数量通过添加CO2而减少。另一方面，添加ISO没有显着的影响。我们的研究结果提供了一个解释在细胞水平上的麻醉依赖性观察任务诱导的BOLD和静息状态连接的先前研究。它们进一步为给定的模式组合提供了适当麻醉方案的选择。
Most studies involving BOLD fMRI in basic neuroscience research are conducted with anesthetized animals. This study investigates neural and hemodynamic activity through a combination of experiments comprising BOLD fMRI, optical calcium recordings and ASL in vivo. Patch clamp experiments of neurons were conducted to evaluate electrophysiological correlates of neural activity in vitro. Various anesthetic conditions embracing numerous anesthetic depths evoked by different concentrations of isoflurane (ISO) and different degrees of hypercapnia under a constant stimulus were investigated. We observed that different anesthetic conditions had major impact on the results obtained, particularly that anesthesia could cause a massive divergence of different experimental modalities.In ventilated animals, robust BOLD responses were detectable even with relatively deep anesthesia, while in non-ventilated animals, BOLD responses were not detectable under these conditions. This was most likely due to hypercapnia caused by respiratory depression, as in ventilated animals administered CO2had the same effect. This observation agreed with measurements of perfusion, which showed that inhaled CO2increased perfusion significantly, while ISO did not.In optical calcium measurements, higher concentrations of ISO decreased spontaneous neural activity, but not stimulus-evoked responses. This observation was explained by a generally lower excitability of neurons under ISO, which suppressed spontaneous activity, and consequently left more neurons available to fire synchronously in response to a stimulus. Interpreting this phenomenon as an integrated signal of independent single neurons was supported by patch clamp experiments as the number of action potentials (APs) per stimulus was decreased by addition of CO2. Addition of ISO on the other hand had no significant effect.Our results provide an explanation on the cellular level for anesthesia-dependent observations in previous studies of task-induced BOLD and resting state connectivity. They further inform selection of the adequate anesthetic regimen for a given combination of modalities.