Activity-dependent plasticity is a fundamental requirement for human motor learning, which takes place at several stages of the motor system and involves various mechanisms in neuronal circuitry. Here, we investigate parameters of cortical and spinal excitability before and immediately after a single session of locomotion-like arm training (LMT) or sequential visuo-motor learning (VMT). Both training paradigms focused especially on mainly activating the flexor carpi radialis muscle (FCR). The activity-dependent change in the excitability of FCR-associated neurons was investigated using standard transcranial magnetic stimulation, including analysis of motor-evoked potentials (MEP) amplitude, short-interval intracortical inhibition and intracortical facilitation (ICF). Furthermore, spinal plasticity was also assessed by means of homosynaptic FCR H-reflex depression (HD). LMT decreased HD and ICF. In contrast, VMT had no significant effect on cortical and spinal parameters. There was a nonsignificant tendency of an increase in MEP amplitudes after both interventions. This implies that human locomotor-related learning involves spinal mechanisms. Despite the decreasing importance of quadrupedal coordination in the course of evolution, these changes in transsynaptic plasticity may reflect a persisting locomotor memory-encoding function in the spinal circuitry of the human upper extremities. Evaluating FCR HD might be helpful for the evaluation and development of locomotor rehabilitation strategies.