Probabilistic inference of Homonymous and Heteronymous Recurrent Inhibition in Human Muscles from Large-Scale Motor Neuron Recordings

Understanding how spinal circuits shape motor neuron behavior during muscle contractions remains a major challenge. Here, we combined large-scale motor unit recordings with simulation-based inference to generate probabilistic estimates of homonymous and heteronymous recurrent inhibition, a key spinal circuit that has remained largely inaccessible during natural voluntary contractions. We constructed synchronization cross-histograms from motor neuron spike trains and extracted features representative of recurrent inhibition. Because these features are also influenced by higher-frequency components of common synaptic input, we developed a simulation-based inference framework to disentangle these effects. Following validation, we applied this framework to experimental data from six muscles at two contraction intensities, revealing previously uncharacterized muscle-and intensity-dependent patterns: recurrent inhibition decreased with contraction intensity in most muscles but increased in the vastus lateralis and medialis. The pipeline is openly available and designed for reuse on comparable datasets and for adaptation to diverse experimental contexts, including other spinal circuits. Teaser Large-scale motor-unit recordings enable in-vivo probabilistic mapping of spinal recurrent inhibition.