The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling

Costa, Ana Rita; Pinto‐Costa, Rita; Sousa, Sara; Sousa, Mónica Mendes

doi:10.3389/fnmol.2018.00319

Cited by 58 publications

(44 citation statements)

References 75 publications

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“…Reduced ADs were also observed at Nodes of Ranvier, as described in the literature. It has been described that AD is regulated by the axonal cytoskeleton 38 , which maintains axon shape and consists of nanometer thick neurofilaments. Decreases in AD have been shown to occur when axons are subjected to axial or circumferential tension, or microtubule disruption 39 .…”

Section: Changes To Axonal Morphology May Be Caused By Extra-axonal Omentioning

confidence: 99%

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

Andersson

Kjer

Rafael-Patiño

et al. 2020

Preprint

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Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Non-invasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires 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 variance 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. 4 acquired diffusion signal 15 . However, diffusion MRI-based AD estimates 14,16,17 are larger than those obtained by histology 15,18 . A potential cause is inaccurate modeling of the WM compartments, including the century old representation of myelinated axons as cylinders. A validation of the 3D WM anatomy could thus improve diffusion MRI-based AD estimations 17 and shed light on the validity of enforcing a cylindrical geometry and constant g-ratio in axonal structure-function relations. Recent 3D electron microscopy (EM) studies on axon morphology of the mouse reveal, in high resolution, non-uniform ADs and trajectories 19,20 . However, axons are only tracked for up to 20 µm, a fraction of their length in MRI voxels. Here, we characterize the long-range micro-morphologies of axons against the backdrop of the complex 3D WM environment consisting of blood vessels, cells and vacuoles. With synchrotron X-ray Nano-Holotomography (XNH), we acquire MRI measurements of the WM from the same monkey brain as in Alexander et al. (2010) 14 and Dyrby et al. (2013) 21 , in which the MRIderived AD estimates were larger than those estimated by histology. The 3D WM environment is mapped at a voxel size of 75 nm and volume of approximately 150 ⨉ 150 ⨉ 150 µm 3 . By combining adjacent XNH volumes, we extract axons >660 µm in length and show that AD, axon trajectory and g-ratio depend on the local microstructural environment. The 3D measurements shed light on the interpretation of 2D measurements, highlighting the importance of the third dimension for a robust description of single-axon structure and function. Lastly, by performing Monte Carlo (MC) diffusion simulations on axonal substrates with morphological features deriving from the XNH-segmented axons, we show that geometrical deviations from cylinders cause an overestimation of AD with diffusion MRI.

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Section: Changes To Axonal Morphology May Be Caused By Extra-axonal Omentioning

confidence: 99%

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

Andersson

Kjer

Rafael-Patiño

et al. 2020

Preprint

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“…Oligodendrocytes commence the myelination of a nearby axon when: (a) the axon has a larger diameter than roughly 0.5 micrometres (Nave and Werner, 2014); and/or (b) a sufficient number of action potentials have passed along the unmyelinated axon. The passage of action potentials itself can promote an increase of axon diameter (Costa et al, 2018) so that activity might be ultimately considered the primary driver of myelination. Once an axon is myelinated, several mechanisms are available to fine-tune the conduction velocity, a control needed to ensure the arrival-time synchrony of action potentials at synaptic destinations.…”

Section: The Process Of Myelinationmentioning

confidence: 99%

Myelin and Modeling: Bootstrapping Cortical Microcircuits

Turner

2019

Front. Neural Circuits

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Histological studies of myelin-stained sectioned cadaver brain and in vivo myelin-weighted magnetic resonance imaging (MRI) show that the cerebral cortex is organized into cortical areas with generally well-defined boundaries, which have consistent internal patterns of myelination. The process of myelination is largely driven by neural experience, in which the axonal passage of action potentials stimulates neighboring oligodendrocytes to perform their task. This bootstrapping process, such that the traffic of action potentials facilitates increased traffic, suggests the hypothesis that the specific pattern of myelination (myeloarchitecture) in each cortical area reveals the principal cortical microcircuits required for the function of that area. If this idea is correct, the observable sequential maturation of specific brain areas can provide evidence for models of the stages of cognitive development.

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“…This finding furthers elucidates the mechanism of activity-dependent structural plasticity of the AIS (Figure 3). Of note, it has long been know that axon diameter is regulated by activity-dependent mechanisms as axons swell during the generation of an action potential (reviewed in [106] and [107]). Later, NMII activity was also shown to be involved in axonal electrophysiology as blebbistatin increases action potential conduction velocities in hipppocampal neuron cultures [99].…”

Section: Why Is Active Nmii Enriched In the Ais?mentioning

confidence: 99%

Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

Costa¹,

Sousa²

2020

Cells

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By binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in the adult), radial and longitudinal axonal tension, and synapse formation and function. In this review, we discuss the current knowledge on the spatial distribution and function of the actomyosin cytoskeleton in different axonal compartments. We highlight some of the apparent contradictions and open questions in the field, including the role of NMII in the regulation of axon growth and regeneration, the possibility that NMII structural arrangement along the axon shaft may control both radial and longitudinal contractility, and the mechanism and functional purpose underlying NMII enrichment in the axon initial segment. With the advances in live cell imaging and super resolution microscopy, it is expected that in the near future the spatial distribution of NMII in the axon, and the mechanisms by which it participates in axonal biology will be further untangled.

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The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling

Cited by 58 publications

References 75 publications

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

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

Myelin and Modeling: Bootstrapping Cortical Microcircuits

Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

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