INTRODUCTION: In Amyotrophic Lateral Sclerosis (ALS), the electrophysiological profile of spinal motoneurons (MNs) undergoes drastic alterations, marking the hallmark for their degeneration. Transcutaneous spinal direct current stimulation (tsDCS) is a neuromodulation method that evokes long-term neuroplasticity in MNs. We have recently demonstrated that chronic tsDCS alters spinal MN synaptic excitation levels in a polarity-dependent manner.

AIM(S): Here, we expand our investigations to determine if spinal MNs' membrane, threshold, and firing properties are also affected by chronic tsDCS.

METHOD(S): Presympthomatic p35-p40 SOD1 G93A mice were exposed to anodal, cathodal, or sham tsDCS of 60 µA for 15 minutes for 10 days under isofluorane anesthesia. In vivo intracellular recordings of MNs were performed at p45-p50, and the MNs' electrophysiological profile was analysed.

RESULTS: Following anodal tsDCS, a significant reduction in the MNs' plateau input resistance and firing gain was observed. Conversely, cathodal tsDCS did not change MNs' input resistance but increased their membrane time constant and reduced the rheobase and Ion current. Surprisingly, both anodal and cathodal tsDCS increased the MNs' SAG ratio. The polarization-dependent changes in the electrophysiological profile of MNs significantly influenced their population behavior. After anodal polarization, a notably larger proportion of MNs were able to reach a primary range of firing in response to depolarizing ramps of current. In contrast, following cathodal polarization, more cells could generate action potentials during ramp current injection but without reaching the primary firing range.

CONCLUSIONS: These results highlight the differential effects of 10 days of anodal and cathodal tsDCS on MN electrophysiological profile in ALS.

FINANCIAL SUPPORT: This research was supported by Polish National Science Centre grants 2019/35/B/NZ4/02058 and 2022/04/Y/NZ4/00117.