Cervical dorsal rhizotomy enhances serotonergic innervation of phrenic motoneurons and serotonin-dependent long-term facilitation of respiratory motor output in rats.
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 micrometer 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.
Kinkead
R
R
Unité de Recherche en Pédiatrie, Centre Hôspitalier Universitaire de Québec, Pavillon St-François d'Assise, Québec, QC G1L 3L5 Canada.
Zhan
W Z
WZ
Prakash
Y S
YS
Bach
K B
KB
Sieck
G C
GC
Mitchell
G S
GS
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D048429:Cell Size / Q000502:physiology; D002772:Cholera Toxin; D003712:Dendrites / Q000737:chemistry / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology; D010507:Periodicity; D010791:Phrenic Nerve / Q000737:chemistry / Q000166:cytology* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D019051:Rhizotomy; D012701:Serotonin / Q000502:physiology*
D012701:Serotonin; D002772:Cholera Toxin