Spatial and network principles behind neural generation of locomotion

Abstract

Generation of locomotion is a fundamental function of the spinal cord, yet the underlying principles remain unclear. In particular, the relationship between neuronal cell types, networks and function has been difficult to establish. Here, we propose principles by which functions arise primarily from spatial features of the cord. First, we suggest that distinct cell types with dissimilar length of projection constitute an asymmetrical "Mexican hat" topology, i.e. local excitation and surrounding inhibition, along the rostro-caudal axis. Second, the transversal segregation of cell types conveniently allows synapses to form with appropriate targets. We demonstrate these principles in a model of the mouse spinal cord, where networks are constructed by probabilistic sampling of synaptic connections from cell-specific projection patterns, which are gleaned from literature. The cell-type distributions are derived from single-cell RNA sequencing combined with spatial transcriptomics. We find that essential aspects of locomotion are recapitulated and easily controlled, and several experimental observations can now be explained mechanistically. Further, two main features are predicted: propagating bumps of neural activity and asymmetric neuronal projections with local excitation and wider inhibition. Besides linking cell types, structure and function, our approach provides a unifying framework for understanding motor activity across limbed and undulatory species.