Uncovering the biology of myelin with optical imaging of the live brain

Abstract

Myelin has traditionally been considered a static structure that is produced and assembled during early developmental stages. While this characterization is accurate in some contexts, recent studies have revealed that oligodendrocyte generation and patterns of myelination are dynamic and potentially modifiable throughout life. Unique structural and biochemical properties of the myelin sheath provide opportunities for the development and implementation of multimodal label‐free and fluorescence optical imaging approaches. When combined with genetically encoded fluorescent tags targeted to distinct cells and subcellular structures, these techniques offer a powerful methodological toolbox for uncovering mechanisms of myelin generation and plasticity in the live brain. Here, we discuss recent advances in these approaches that have allowed the discovery of several forms of myelin plasticity in developing and adult nervous systems. Using these techniques, long‐standing questions related to myelin generation, remodeling, and degeneration can now be addressed.

Emerging technologies to study glial cells

“…These techniques have unique advantages, such as chemical sensitivity for myelin lipids with CARS (H. Wang et al, 2005) and deep tissue imaging capability, that can reach subcortical white matter, with THG (Farrar et al, 2011). However, these techniques are not easy to implement, and require sophisticated equipment and setups not readily available in most laboratories (reviewed in (Hill & Grutzendler, 2019). In contrast, spectral confocal reflectance microscopy (SCoRe) is a recently developed, simple, but yet powerful method for high-resolution intravital label free imaging of myelinated axons in the mammalian brain (Schain, Hill, & Grutzendler, 2014).…”

In Vivo Simultaneous Nonlinear Absorption Raman and Fluorescence (SNARF) Imaging of Mouse Brain Cortical Structures

“…Nonetheless, abnormalities in myelin structure, such as myelin swelling and ballooning, have been implicated in cognitive slowing. 48 With its spectroscopic imaging and quantitative capability, SNARF microscopy offers a powerful alternative approach for investigating myelin degeneration and regeneration.…”

Absence of R‐Ras1 and R‐Ras2 causes mitochondrial alterations that trigger axonal degeneration in a hypomyelinating disease model

“…OLs are generated from oligodendrocyte progenitor cells (OPCs), characterized by different migratory capacities, morphological complexity, gene expression pattern, and specific marker expressions (Foerster, Hill, & Franklin, 2019;Sock & Wegner, 2019). After differentiating from OPCs, mature OLs create myelin and extend the processes that wrap around axons to form compact myelin sheaths (Foster, Bujalka, & Emery, 2019;Hill & Grutzendler, 2019;Snaidero & Simons, 2017).…”