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The (Un)Conscious Mouse as a Model for Human Brain Functions: Key Principles of Anesthesia and Their Impact on Translational Neuroimaging
Frontiers in Systems Neuroscience ( IF 3 ) Pub Date : 2020-05-19 , DOI: 10.3389/fnsys.2020.00008
Henning M Reimann 1 , Thoralf Niendorf 1, 2
Affiliation  

In recent years, technical and procedural advances have brought functional magnetic resonance imaging (fMRI) to the field of murine neuroscience. Due to its unique capacity to measure functional activity non-invasively, across the entire brain, fMRI allows for the direct comparison of large-scale murine and human brain functions. This opens an avenue for bidirectional translational strategies to address fundamental questions ranging from neurological disorders to the nature of consciousness. The key challenges of murine fMRI are: (1) to generate and maintain functional brain states that approximate those of calm and relaxed human volunteers, while (2) preserving neurovascular coupling and physiological baseline conditions. Low-dose anesthetic protocols are commonly applied in murine functional brain studies to prevent stress and facilitate a calm and relaxed condition among animals. Yet, current mono-anesthesia has been shown to impair neural transmission and hemodynamic integrity. By linking the current state of murine electrophysiology, Ca2+ imaging and fMRI of anesthetic effects to findings from human studies, this systematic review proposes general principles to design, apply and monitor anesthetic protocols in a more sophisticated way. The further development of balanced multimodal anesthesia, combining two or more drugs with complementary modes of action helps to shape and maintain specific brain states and relevant aspects of murine physiology. Functional connectivity and its dynamic repertoire as assessed by fMRI can be used to make inferences about cortical states and provide additional information about whole-brain functional dynamics. Based on this, a simple and comprehensive functional neurosignature pattern can be determined for use in defining brain states and anesthetic depth in rest and in response to stimuli. Such a signature can be evaluated and shared between labs to indicate the brain state of a mouse during experiments, an important step toward translating findings across species.

中文翻译:

作为人类大脑功能模型的(无意识)小鼠:麻醉的关键原则及其对转化神经成像的影响

近年来,技术和程序的进步将功能性磁共振成像 (fMRI) 带入了小鼠神经科学领域。由于其在整个大脑中无创测量功能活动的独特能力,fMRI 允许直接比较大规模的小鼠和人类大脑功能。这为双向转化策略开辟了一条途径,以解决从神经系统疾病到意识本质的基本问题。小鼠 fMRI 的主要挑战是:(1) 产生和维持接近平静和放松的人类志愿者的大脑功能状态,同时 (2) 保持神经血管耦合和生理基线条件。低剂量麻醉方案通常用于小鼠功能性大脑研究,以防止压力并促进动物之间的平静和放松状态。然而,目前的单麻醉已被证明会损害神经传递和血流动力学完整性。通过将小鼠电生理学、Ca2+ 成像和麻醉效应 fMRI 的当前状态与人类研究的结果联系起来,本系统综述提出了以更复杂的方式设计、应用和监测麻醉方案的一般原则。平衡多模式麻醉的进一步发展,将两种或多种药物与互补的作用模式相结合,有助于塑造和维持特定的大脑状态和鼠生理学的相关方面。通过 fMRI 评估的功能连接及其动态库可用于推断皮质状态并提供有关全脑功能动态的附加信息。在此基础上,可以确定一个简单而全面的功能神经特征模式,用于定义大脑状态和静止状态和对刺激的反应的麻醉深度。这样的签名可以在实验室之间进行评估和共享,以指示实验期间小鼠的大脑状态,这是跨物种转化研究结果的重要一步。
更新日期:2020-05-19
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