Computational Modeling of Spinal Locomotor Circuitry in the Age of Molecular Genetics

Int J Mol Sci. 2021 Jun 25;22(13):6835. doi: 10.3390/ijms22136835.

Abstract

Neuronal circuits in the spinal cord are essential for the control of locomotion. They integrate supraspinal commands and afferent feedback signals to produce coordinated rhythmic muscle activations necessary for stable locomotion. For several decades, computational modeling has complemented experimental studies by providing a mechanistic rationale for experimental observations and by deriving experimentally testable predictions. This symbiotic relationship between experimental and computational approaches has resulted in numerous fundamental insights. With recent advances in molecular and genetic methods, it has become possible to manipulate specific constituent elements of the spinal circuitry and relate them to locomotor behavior. This has led to computational modeling studies investigating mechanisms at the level of genetically defined neuronal populations and their interactions. We review literature on the spinal locomotor circuitry from a computational perspective. By reviewing examples leading up to and in the age of molecular genetics, we demonstrate the importance of computational modeling and its interactions with experiments. Moving forward, neuromechanical models with neuronal circuitry modeled at the level of genetically defined neuronal populations will be required to further unravel the mechanisms by which neuronal interactions lead to locomotor behavior.

Keywords: central pattern generator; computational modeling; interneurons; neuronal control of locomotion; sensory feedback; spinal cord.

Publication types

  • Review

MeSH terms

  • Animals
  • Feedback, Sensory
  • Genetic Association Studies*
  • Humans
  • Interneurons / physiology
  • Locomotion*
  • Models, Neurological*
  • Motor Neurons / physiology*
  • Spinal Cord / physiology*