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The Journal of Neuroscience, April 1, 2003, 23(7):2993

Synaptic Pathways to Phrenic Motoneurons Are Enhanced by Chronic Intermittent Hypoxia after Cervical Spinal Cord Injury

David D. Fuller¹, Stephen M. Johnson¹, E. Burdette Olson Jr², and Gordon S. Mitchell¹

Departments of ¹ Comparative Biosciences and ² Preventive Medicine, University of Wisconsin, Madison, Wisconsin 53706

Spinal hemisection at C2 reveals caudal synaptic pathways that cross the spinal midline (crossed phrenic pathways) and can restore inspiratory activity in ipsilateral phrenic motoneurons. Intermittent hypoxia induces plasticity in the cervical spinal cord, resulting in enhanced inspiratory phrenic motor output. We hypothesized that chronic intermittent hypoxia (CIH) (alternating 11% O₂ and air; 5 min periods; 12 hr per night; 7 nights) would strengthen crossed phrenic pathways. Experiments were performed on anesthetized, vagotomized, paralyzed, ventilated, and spinally injured (C2 hemisection) rats that were exposed to either normoxia or CIH before acute injury (preconditioning) or after chronic injury (postconditioning). Spontaneous inspiratory bursts or compound action potentials evoked via stimulation of the ventrolateral funiculus (contralateral to injury) were recorded in both phrenic nerves. Spontaneous or evoked activity in crossed phrenic pathways were minimal or absent in all acutely injured rats regardless of preconditioning. In rats postconditioned with normoxia, crossed phrenic inspiratory bursts were observed occasionally during baseline conditions and always during chemoreceptor stimulation (hypoxia and hypercapnia). However, CIH postconditioned rats had substantially larger crossed phrenic inspiratory bursts during baseline, hypoxia, and hypercapnia (all p < 0.05 vs normoxic group). Short-latency (0.7 msec) evoked crossed phrenic potentials were also enhanced by CIH conditioning in chronically injured rats (p < 0.05). We conclude that CIH induced spinal cord plasticity-enhanced phrenic motor output. This plasticity required preconditions established by chronic spinal injury.

Key words: plasticity; crossed phrenic phenomenon; respiratory control; spinal cord injury; C2 hemisection; intermittent hypoxia

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2372993-08$05.00/0

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