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The Journal of Neuroscience, October 15, 1998, 18(20):8436-8443

Cervical Dorsal Rhizotomy Enhances Serotonergic Innervation of Phrenic Motoneurons and Serotonin-Dependent Long-Term Facilitation of Respiratory Motor Output in Rats

Richard Kinkead3, Wen-Zhi Zhan2, Y. S. Prakash2, Karen B. Bach1, Gary C. Sieck2, and Gordon S. Mitchell1

1 Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, 2 Department of Anesthesiology and Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905, and 3 Unité de Recherche en Pédiatrie, Centre Hôspitalier Universitaire de Québec, Pavillon St-François d'Assise, Québec, QC G1L 3L5 Canada

We tested the hypothesis that spinal plasticity elicited by chronic bilateral cervical dorsal rhizotomy (C3-C5; CDR) has functional implications for respiratory motor control. Surgery was performed on rats (CDR or sham-operated) 26 d before phrenic motoneurons were retrogradely labeled with cholera toxin. Rats were killed 2 d later, and their spinal cords were harvested and processed to reveal the cholera toxin-labeled phrenic motoneurons and serotonin-immunoreactive terminals. The number of serotonin-immunoreactive terminals within 5 µm of labeled phrenic motoneuron soma and primary dendrites increased 2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses to hypoxia were compared among CDR, sham-operated, and control rats. Anesthetized, paralyzed, vagotomized, and artificially ventilated rats were exposed to three, 5 min episodes of isocapnic hypoxia (FiO2 = 0.11), separated by 5 min hyperoxic intervals (FiO2 = 0.5). One hour after hypoxia, a long-lasting, serotonin-dependent enhancement of phrenic motor output (long-term facilitation) was observed in both sham and control rats. After CDR, long-term facilitation was 108 and 163% greater than control and sham responses, respectively. Pretreatment of CDR rats with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v.) before episodic hypoxia prevented long-term facilitation and revealed a modest (-28 ± 13%; p < 0.05) long-lasting depression of phrenic motor output. The results indicate that CDR: (1) increases serotonergic innervation of the phrenic motor nucleus; and (2) augments serotonin-dependent long-term facilitation of phrenic motor output. These results further suggest a form of plasticity based on changes in the capacity for neuromodulation.

Key words: plasticity; serotonin; respiratory control; long-term facilitation; rhizotomy; phrenic motoneurons


Copyright © 1998 Society for Neuroscience  0270-6474/98/18208436-08$05.00/0


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