Abstract
The timing of transcranial direct current stimulation (tDCS) relative to motor practice may influence its behavioral effects, but the accompanying molecular responses remain incompletely characterized. Here, we examined cortical current delivery, rotarod performance, and BDNF-TrkB signaling in mice receiving anodal tDCS concurrently with training or during intertrial intervals. Cortical current measurements indicated that approximately half of the applied current reached the measurement site under the experimental stimulation configuration. During four days of rotarod training, anodal tDCS concurrent with motor tasks improved performance at selected trials and increased footstep frequency, whereas stimulation delivered before or after training trials did not significantly improve performance. Preceding online anodal tDCS with cathodal stimulation provided no detectable additional behavioral benefit. Concurrent anodal tDCS increased TrkB phosphorylation in the stimulated cortex after both one and four days, without a significant increase in BDNF levels. Paused offline anodal tDCS stimulation also increased TrkB phosphorylation after one day despite lacking a detectable behavioral benefit. No significant molecular changes were detected in the sampled non-targeted brain regions. Genetic experiments revealed reduced rotarod performance in BDNF heterozygous mice at several trials and trial-dependent responses to online stimulation in BDNF-KIV mice. Together, these findings show that concurrent anodal tDCS improves rotarod performance and increases TrkB phosphorylation in the stimulated cortex. These results motivate further investigation of how BDNF-TrkB signaling interacts with task-related neural activity during stimulation.