title: Light-induced rescue of breathing after spinal cord injury.
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.
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Alilain
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Horn
authors.forename: Rishi
authors.initials: R
authors.lastname: Dhingra
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dick
authors.forename: Stefan
authors.initials: S
authors.lastname: Herlitze
authors.forename: Jerry
authors.initials: J
authors.lastname: Silver
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D003964:Diaphragm / Q000294:innervation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000502:physiology / Q000528:radiation effects; D010243:Paralysis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010507:Periodicity; D010789:Phototherapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012119:Respiration / Q000528:radiation effects*; D012131:Respiratory Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D012243:Rhodopsin / Q000378:metabolism / Q000528:radiation effects; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012243:Rhodopsin