Poster abstracts

Poster number 17 submitted by Di Ma

Three-dimensional ultrastructural adaptation of central axons regulated by their mechanical microenvironment

Di Ma (OSBP), Binbin Deng (Center for Electron Microscopy and Analysis), Chao Sun (MCDB), David W McComb (Center for Electron Microscopy and Analysis), Chen Gu (Department of Biological Chemistry and Pharmacology)

Abstract:
Axon shafts mediate unidirectional conduction of action potentials and long-distance transport of proteins and organelles from neuronal soma to its synaptic terminals. How these long slender structures are regulated mechanically remains poorly understood. Combining confocal microscopy and cryo-electron tomography (Cryo-ET) with in vivo and in vitro systems, we report that nonuniform mechanical interactions with the microenvironment can lead to more than 10-fold diameter enlargement in an axon of the central nervous system (CNS). In the normal brain of adult Thy1-YFP transgenic mice, individual axons in the cortex displayed significantly higher diameter variation than those in the corpus callosum. When being cultured on lacey carbon film of electron microscopy (EM) grids, CNS axons formed varicosities preferentially in holes, with enriched mitochondria, multivesicular bodies (MVBs), and small vesicles, similar to axonal varicosities induced by mild fluid puffing. Microtubules (MTs) remained constant in all of our Cryo-ET varicosities and were asymmetrically separated at axon branch points often with de novo formation. When axons were fasciculated mimicking in vivo axonal bundles in white matter, varicosity levels reduced. Taken together, our results have revealed several novel features of three-dimensional ultrastructures of central axons in response to the nonuniform microenvironment.

References:
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Keywords: Axonal varicosity, Cryo-electron tomography (Cryo-ET), Axon