Light-induced rescue of breathing after spinal cord injury

Warren J. Alilain, Xiang Li, Kevin P. Horn, Rishi Dhingra, Thomas E. Dick, Stefan Herlitze, Jerry Silver

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

Paralysis is a major consequence of spinal cord injury (SCI). After cervical SCI, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. Expression of channelrhodopsin-2 (ChR2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. We hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express ChR2, photostimulation would restore respiratory motor function in cervical SCI adult animals. Here we show that light activation of ChR2-expressing animals was sufficient to bring about recovery of respiratory diaphragmatic motor activity. Furthermore, robust rhythmic activity persisted long after photostimulation had ceased. This recovery was accomplished through a form of respiratory plasticity and spinal adaptation which is NMDA receptor dependent. These data suggest a novel, minimally invasive therapeutic avenue to exercise denervated circuitry and/or restore motor function after SCI.

Original languageEnglish
Pages (from-to)11862-11870
Number of pages9
JournalJournal of Neuroscience
Volume28
Issue number46
DOIs
StatePublished - Nov 12 2008

Keywords

  • Kindling
  • Motor neuron
  • Nmda receptor
  • Paralysis
  • Plasticity
  • Respiration
  • Spinal cord injury

ASJC Scopus subject areas

  • General Neuroscience

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