Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship.

Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship.
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DOI:
10.1073/pnas.2012533117
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发表时间:
2020-12-29
影响因子:
11.1
通讯作者:
Dyrby TB
Dyrby TB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Andersson M;Kjer HM;Rafael-Patino J;Pacureanu A;Pakkenberg B;Thiran JP;Ptito M;Bech M;Bjorholm Dahl A;Andersen Dahl V;Dyrby TB

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轴突是大脑的通讯电缆,自1860年被发现以来一直被描述为圆柱体。它们的结构与它们传导信号的速度有关,因此可以指示大脑的健康和功能。在这里,我们展示了轴突的微形态和其他轴突外结构之间的相互作用,表明轴突是非圆柱形的,并表现出与环境相关的直径和轨迹变化。直径的非特异性,以及传导速度,挑战了目前关于轴突如何传递信号的知识。扩散磁共振成像可以用来测量活着的大脑中的轴突直径,以探索大脑网络和检测潜在的疾病生物标志物,但我们在这里表明,观察到的轴突的复杂形态偏离了这些测量。轴突传导速度与轴突直径有关,是保证脑网络高效运转的重要因素。体内轴突直径的非侵入性估计可以通过扩散磁共振成像进行,但这项技术需要三维(3D)验证。在这里,高分辨率,3D同步辐射X射线纳米全息断层扫描图像的白质样本从猴子的大脑显示血管,细胞和空泡影响轴突直径和轨迹。在单个轴突内,我们发现直径和传导速度的变化与平均直径相关,这对较大轴突的精确直径测定的价值提出了质疑。这些复杂的3D轴突形态推动了先前报道的轴突直径和g比率的2D趋势。此外,我们发现这些形态偏离了扩散磁共振成像对轴突直径的估计,并最终影响了轴突结构-功能关系的研究和制定。
Axons, the brain’s communication cables, have been described as cylinders since their discovery in 1860. Their structure is linked to how fast they conduct signals and is thus indicative of brain health and function. Here, we demonstrate an interplay between the micromorphology of axons and other extra-axonal structures, showing that axons are noncylindrical and exhibit environment-dependent diameter and trajectory variations. The nonspecificity in diameter, and thus conduction velocity, challenges the current knowledge of how axons communicate signals. Diffusion magnetic resonance imaging can be used to measure axon diameter in the living brain in order to explore the brain network and detect potential biomarkers of disease, but we show here that the observed complex morphologies of axons bias these measurements. Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure–function relationship.
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