Spatial and network principles behind neural generation of locomotion

Area of Science:

• Neuroscience
• Computational Biology
• Systems Neuroscience

Background:

• Understanding the neural basis of locomotion is crucial, yet the precise relationship between neuronal cell types, networks, and function remains elusive.
• The spinal cord's role in generating rhythmic motor patterns, like walking, is fundamental but not fully elucidated.
• Establishing links between specific neuronal populations, their connectivity, and resulting behaviors is a key challenge in neuroscience.

Purpose of the Study:

• To propose and validate that the spatial organization of the spinal cord dictates network-driven locomotor rhythms and patterns.
• To investigate how asymmetric connectivity and cell type segregation contribute to motor control.
• To develop a computational model of the mouse spinal cord to extract and test these spatial principles.

Main Methods:

• Development of a computational model of the mouse spinal cord.
• Probabilistic sampling of synaptic connections based on cell-specific projection patterns from single-cell RNA sequencing and spatial transcriptomics data.
• Analysis of network dynamics to identify principles governing locomotor rhythms and patterns.

Main Results:

• Demonstration that an asymmetric "Mexican hat" connectivity (local excitation, long-range inhibition, longitudinal skew) drives proper motor dynamics.
• Evidence that transversal segregation of cell types facilitates target finding for descending fibers and controls network dynamics.
• Successful induction and control of essential locomotion aspects with minimal parameter optimization.
• Prediction of propagating activity bumps during rhythmic movement.

Conclusions:

• The spatial organization of the spinal cord, characterized by specific connectivity patterns and cell type arrangements, is a key determinant of locomotor control.
• These findings reveal universal spatial principles that link neuronal cell types, their connectivity, and behavioral output across different species.
• This work provides a framework for understanding how neural structure gives rise to complex motor functions.