Recurrent inhibition crosses the spinal cord midline in humans

Abstract

Recurrent inhibition is known to modulate motoneuron output within an active motor pool, but it is unclear whether Renshaw cells receive projections from a contralateral pathway. Using intramuscular single motor unit recordings in humans, we demonstrated that electrical activation of the contralateral quadriceps motor axons elicits a robust decrease in soleus motor unit discharge rate, consistent with the characteristic features of recurrent inhibition. The duration of the inhibition scaled with motor unit firing rates and exhibited substantial interindividual variability. To uncover the underlying circuitry, we developed a biophysically grounded spiking network model constrained by individual experimental data. The model reproduced the observed contralateral inhibitory dynamics only when incorporating a polysynaptic commissural pathway mediated by V3-like interneurons. Model-based inference further revealed that intrinsic motoneuron properties critically shape the duration of inhibition. Together, these findings provide the first evidence for a commissural pathway influencing human spinal recurrent inhibitory networks, revealing a previously unrecognized mechanism that may contribute to bilateral motor coordination.