PUBLICATION

An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish

Authors
Huang, C.X., Zhao, Y., Mao, J., Wang, Z., Xu, L., Cheng, J., Guan, N.N., Song, J.
ID
ZDB-PUB-211211-9
Date
2021
Source
Nature communications   12: 7093 (Journal)
Registered Authors
Keywords
none
Datasets
GEO:GSE182869, GEO:GSE182911, GEO:GSE182868
MeSH Terms
  • Animals
  • Axons/physiology*
  • Electrophysiology
  • Interneurons
  • Locomotion
  • Receptors, Serotonin/genetics
  • Receptors, Serotonin/metabolism
  • Recovery of Function*
  • Serotonergic Neurons/pathology
  • Serotonergic Neurons/physiology*
  • Serotonin/metabolism
  • Spinal Cord/physiopathology
  • Spinal Cord Injuries*/genetics
  • Spinal Cord Injuries*/metabolism
  • Spinal Cord Injuries*/pathology
  • Zebrafish
PubMed
34876587 Full text @ Nat. Commun.
Abstract
Spinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration. Here, we use a two-cut SCI model to investigate whether recovery of locomotion can occur independently of supraspinal connections. Using this injury model, we show that injury induces the localization of a specialized group of intraspinal serotonergic neurons (ISNs), with distinctive molecular and cellular properties, at the injury site. This subpopulation of ISNs have hyperactive terminal varicosities constantly releasing serotonin activating 5-HT1B receptors, resulting in axonal regrowth of spinal interneurons. Axon regrowth of excitatory interneurons is more pronounced compared to inhibitory interneurons. Knock-out of htr1b prevents axon regrowth of spinal excitatory interneurons, negatively affecting coordination of rostral-caudal body movements and restoration of locomotor function. On the other hand, treatment with 5-HT1B receptor agonizts promotes functional recovery following SCI. In summary, our data show an intraspinal mechanism where a subpopulation of ISNs stimulates axonal regrowth resulting in improved recovery of locomotor functions following SCI in zebrafish.
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