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Locomotion-related propriospinal V3 interneurons modulate sensory-transmission to motoneurons by generating primary afferent depolarization

  • Author / Creator
    Lin, Shihao
  • Proprioceptive sensory-evoked reflexes are essential in assisting the precision of basic movements and maintenance of body postures. The motor outputs from these reflexes are precisely calibrated to avoid interfering with the ongoing motor functions. After spinal cord injury (SCI), reflexes become spasms as they are sensitized, over-amplified and prolonged by excessive NMDA signalling. Although a recent study has found that locomotor-related propriospinal V3 interneurons mediate spasms, it remains uncertain how V3 neurons increase reflexes. Using confocal microscopy and electrophysiological recording combined with optogenetic manipulations of V3 neurons, we have found that V3 neurons are the 1st order spinal interneurons of a circuit which is well-known for regulating sensory transmission during reflexes. This circuit generates primary afferent depolarization (PAD) in response to sensory stimulation. That is, sensory inputs monosynaptically activate V3 neurons. Then, V3 neurons produce both an NMDA receptor dependent PAD, by directly releasing glutamate onto sensory afferents, and a GABAA receptor dependent PAD, by indirectly driving GABAergic interneurons that in turn release GABA onto sensory afferents. In this process, long propriospinal axons of V3 neurons allow sensory inputs from one sensory entry point of the spinal cord to generate PAD on both sides of the spinal cord and in many spinal segments above and below this entry point. This V3-evoked PAD amplifies reflexes throughout the spinal cord. After SCI, V3 neurons produce a larger NMDA-mediated PAD. This suggests potential involvements of NMDA dependent PAD in the development of spasms.

  • Subjects / Keywords
  • Graduation date
    Fall 2022
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-r1cx-qm17
  • License
    This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.