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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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