RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Neuron. 2017 Dec 20;96(6):1419-1431.e5. doi: 10.1016/j.neuron.2017.11.011. Epub 2017 Dec 7.

Abstract

Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORβ in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORβ inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. VIDEO ABSTRACT.

Keywords: RORβ; locomotion; motor control; presynaptic inhibition; proprioception; sensory feedback; spinal interneurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways
  • Animals
  • Animals, Newborn
  • Electric Stimulation
  • Feedback, Sensory
  • GABA Agents / pharmacology
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Glycine Plasma Membrane Transport Proteins / genetics
  • Glycine Plasma Membrane Transport Proteins / metabolism
  • Hip Joint / innervation
  • Interneurons / physiology*
  • Locomotion / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Skeletal / physiology
  • Neural Inhibition / genetics
  • Neural Inhibition / physiology
  • Nuclear Receptor Subfamily 1, Group F, Member 2 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 2 / metabolism*
  • PAX2 Transcription Factor / genetics
  • PAX2 Transcription Factor / metabolism
  • Reflex / genetics
  • Reflex / physiology
  • Sensory Thresholds / physiology
  • Spinal Cord / cytology*
  • Walking / physiology*

Substances

  • GABA Agents
  • Glycine Plasma Membrane Transport Proteins
  • Luminescent Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 2
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Rorb protein, mouse
  • Slc6a5 protein, mouse
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1