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The Journal of Neuroscience, November 12, 2008, 28(46):11862-11870; doi:10.1523/JNEUROSCI.3378-08.2008

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Development/Plasticity/Repair
Light-Induced Rescue of Breathing after Spinal Cord Injury

Warren J. Alilain,¹ Xiang Li,¹ Kevin P. Horn,¹ Rishi Dhingra,² Thomas E. Dick,^1,2 Stefan Herlitze,¹ and Jerry Silver¹

¹Department of Neurosciences and ²Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Correspondence should be addressed to Dr. Jerry Silver, Department of Neurosciences, Case Western Reserve University School of Medicine, Room E-658, 2109 Adelbert Road, Cleveland, OH 44106. Email: jxs10{at}case.edu

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.

Key words: spinal cord injury; paralysis; respiration; motor neuron; plasticity; NMDA receptor; kindling

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Received July 18, 2008; revised Sept. 10, 2008; accepted Sept. 14, 2008.

Correspondence should be addressed to Dr. Jerry Silver, Department of Neurosciences, Case Western Reserve University School of Medicine, Room E-658, 2109 Adelbert Road, Cleveland, OH 44106. Email: jxs10{at}case.edu

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