Differential Effects of Invasive Anodal Trans-spinal Direct Current Stimulation on Monosynaptic Excitatory Postsynaptic Potentials, Ia Afferents Excitability, and Motoneuron Intrinsic Properties Between Superoxide Dismutase Type-1 Glycine to Alanine Substitution at Position 93 and Wildtype Mice

Abstract

In presymptomatic amyotrophic lateral sclerosis (ALS), spinal motoneurons (MNs) have reduced firing patterns and synaptic excitation levels. Preliminary data indicated that in the SOD1 G93A mouse model of ALS, monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in spinal MN by Ia proprioceptive afferent stimulation could be facilitated by trans-spinal direct current stimulation (tsDCS). However, which element of the Ia afferent-MN circuit is affected by tsDCS, and whether tsDCS-induced EPSP facilitation is a general phenomenon or specific to the superoxide dismutase type-1 (SOD1) Glycine to Alanine substitution at position 93 (G93A) mutation, remain to be determined. In this study, we have applied 15-minute tsDCS to the lumbar segments of presymptomatic SOD1 and wildtype (WT) mice and explored its impact on MN passive membrane properties, EPSP amplitude, and Ia afferent activity. While anodal tsDCS induced short-lasting EPSP facilitation in both SOD1 and WT mice, Ia afferent activity and passive membrane properties were altered only in SOD1 mice. Interestingly, EPSP amplitudes of SOD1 mice remained facilitated for at least 1 h after current application, but no long-lasting effect was observed in WT mice. Moreover, anodal tsDCS failed to induce any long-lasting changes in MN passive membrane properties in both SOD1 and WT mice. Conversely, cathodal tsDCS decreased Ia afferent induced EPSP amplitudes only during current application in SOD1 MNs, and no significant effects on Ia afferents excitability were observed. Our findings indicate the high susceptibility of SOD1 MNs to tsDCS and highlight the potential of this neuromodulation technique for the treatment of ALS.

Keywords: Ia afferent excitability; amyotrophic lateral sclerosis; electrophysiology; excitatory postsynaptic potential; neuromodulation; passive membrane properties.