Bursting interneurons in the deep dorsal horn develop increased excitability and sensitivity to serotonin after chronic spinal injury

Theeradej Thaweerattanasinp, Derin Birch, Mingchen C. Jiang, Matthew C. Tresch, David J. Bennett, Charles J. Heckman, Vicki M. Tysseling*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

First published March 25, 2020; doi:10.1152/jn.00701.2019.-The loss of descending serotonin (5-HT) to the spinal cord contributes to muscle spasms in chronic spinal cord injury (SCI). Hyperexcitable motoneurons receive long-lasting excitatory postsynaptic potentials (EPSPs), which activate their persistent inward currents to drive muscle spasms. Deep dorsal horn (DDH) neurons with bursting behavior could be involved in triggering the EPSPs due to loss of inhibition in the chronically 5-HT-deprived spinal cord. Previously, in an acutely transected preparation, we found that bursting DDH neurons were affected by administration of the 5-HT1B/1D receptor agonist zolmitriptan, which suppressed their bursts, and by N-methyl-D-aspartate (NMDA), which enhanced their bursting behavior. Non-bursting DDH neurons were not influenced by these agents. In the present study, we investigate the firing characteristics of bursting DDH neurons following chronic spinal transection at T10 level in adult mice and examine the effects of replacing lost endogenous 5-HT with zolmitriptan. Terminal experiments using our in vitro preparation of the sacral cord were carried out ~10 wk postransection. Compared with the acute spinal stage of our previous study, DDH neurons in the chronic stage became more responsive to dorsal root stimulation, with burst duration doubling with chronic injury. The suppressive effects of zolmitriptan were stronger overall, but the facilitative effects of NMDA were weaker. In addition, the onset of DDH neuron activity preceded ventral root output and the firing rates of DDH interneurons correlated with the integrated long-lasting ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following SCI and inhibition by 5-HT. NEW & NOTEWORTHY We investigate the firing characteristics of bursting deep dorsal horn (DDH) neurons following chronic spinal transection. DDH neurons in the chronic stage are different from those in the acute stage as noted by their increase in excitability overall and their differing responses serotonin (5-HT) and N-methyl-D-aspartate (NMDA) receptor agonists. Also, there is a strong relationship between DDH neuron activity and ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following chronic spinal cord injury (SCI).

Original languageEnglish (US)
Pages (from-to)1657-1670
Number of pages14
JournalJournal of neurophysiology
Volume123
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • 5-HT
  • DDH
  • Deep dorsal horn neurons
  • N-methyl-D-aspartate
  • NMDA
  • SCI
  • Serotonin
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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