Abstract

Myelin formation has been identified as a modulator of neural plasticity. New tools are required to investigate the mechanisms by which environmental inputs and neural activity regulate myelination patterns. In this study, we demonstrate a microfluidic compartmentalized culture system with integrated electrical stimulation capabilities that can induce neural activity by whole cell and focal stimulation. A set of electric field simulations was performed to confirm spatial restriction of the electrical input in the compartmentalized culture system. We further demonstrate that electrode localization is a key consideration for generating uniform the stimulation of neuron and oligodendrocytes within the compartments. Using three configurations of the electrodes we tested the effects of subcellular activation of neural activity on distal axon myelination with oligodendrocytes. We further investigated if oligodendrocytes have to be exposed to the electrical field to induce axon myelination. An isolated stimulation of cell bodies and proximal axons had the same effect as an isolated stimulation of distal axons co-cultured with oligodendrocytes, and the two modes had a non-different result than whole cell stimulation. Our platform enabled the demonstration that electrical stimulation enhances oligodendrocyte maturation and myelin formation independent of the input localization and oligodendrocyte exposure to the electrical field.

Highlights

  • Myelin sheaths play pivotal roles as an axon isolator and a conductor of electrical signals in nerve system

  • It has become abundantly clear that the role of myelination in the central nervous system expands beyond expediting electrical signal propagation

  • We present a compartmentalized neuron/oligodendrocyte co-culture device integrated with electrical stimulation system that allows applying whole cell and spatially restricted cell activity induction

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Summary

Introduction

Myelin sheaths play pivotal roles as an axon isolator and a conductor of electrical signals in nerve system. Socially isolated adult mice demonstrated thinner myelin sheaths, lower level of gene expression specific to myelination, and behavioral deficits. The generation of myelin-forming oligodendrocyte (OLs) was shown to correlate with motor learning— teaching a mouse a complex running task increased OLs formation, while a knockout animal with reduced oligodendrogenesis demonstrated impaired learning performance [5]. Those observations are indicative of a link between environmental stimuli, central nervous system (CNS) plasticity and myelination

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