Acute Invasive Dorso-Ventral DCS Applied With a Ball Electrode Does Not Alter Spinal Motoneurons' Firing Characteristics in the SOD-1 G93A Mouse Model of ALS.

Abstract

In amyotrophic lateral sclerosis (ALS), alterations of spinal motoneurons' (MNs) excitability form the hallmark of their degeneration. Trans-spinal direct current stimulation (tsDCS) is based on the delivery of low-intensity DC to the spinal column in order to alter spinal circuit excitability. Recently, this technique was applied to the management of ALS in the SOD1 G93A mice and resulted in a reduction of disease biomarkers and extended mouse survival. While indirect evidence suggests that these effects can be linked to a decrease in MNs excitability following tsDCS, this has never been directly confirmed. Therefore, in this study, we have utilized in vivo sharp intracellular recordings of spinal MN to directly investigate the impact of DC on MN intrinsic excitability in SOD1 G93A mice. Electrophysiological properties of MNs recorded before DCS were compared to the properties of MNs recorded within 1 h after DCS application using linear mixed-effect models. We have found that direct DCS application significantly increases MN peak and plateau input resistance (by 31% and 35%, respectively); however, this was not linked to any significant change to MN threshold and firing properties. Both mathematical modelling and in vivo recordings of the electric field (EF) indicate that our results may be explained by the low density of the EF at the MN recording site. While our results indicate that invasive DCS is not efficient in modifying MN excitability, it may be effective in altering the excitability of afferent fibers traversing the dorsal column close to the DCS application site.