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The Journal of Neuroscience, July 15, 2002, 22(14):6239-6246
Phrenic Long-Term Facilitation Requires Spinal Serotonin Receptor
Activation and Protein Synthesis
Tracy. L.
Baker-Herman and
Gordon S.
Mitchell
Department of Comparative Biosciences and Center for Neuroscience,
University of Wisconsin, Madison, Wisconsin 53706
Respiratory long-term facilitation (LTF) is a form of
serotonin-dependent plasticity induced by intermittent hypoxia. LTF is
manifested as a long-lasting increase in respiratory amplitude (and
frequency) after the hypoxic episodes have ended. We tested the
hypotheses that LTF of phrenic amplitude requires spinal serotonin receptor activation and spinal protein synthesis. A broad-spectrum serotonin receptor antagonist (methysergide) or protein synthesis inhibitors (emetine or cycloheximide) were injected intrathecally in
the cervical spinal cord of anesthetized rats. Control rats, injected
with vehicle (artificial CSF), exhibited an augmented phrenic burst
amplitude after three 5 min episodes of hypoxia (78 ± 15% above
baseline, 60 min after hypoxia; p < 0.05),
indicating LTF. Pretreatment with methysergide, emetine, or
cycloheximide attenuated or abolished phrenic LTF (20 ± 4, 0.2 ± 11, and 20 ± 2%, respectively; all
p > 0.05). With protein synthesis inhibitors, phrenic LTF differed from control by 15 min after intermittent hypoxia.
As an internal control against unintended drug distribution, we
measured respiratory LTF in hypoglossal (XII) motor output. At 60 min
after intermittent hypoxia, all treatment groups exhibited similar XII
LTF (artificial CSF, 44 ± 10%; methysergide, 40 ± 5%;
emetine, 35 ± 9%; and cycloheximide, 57 ± 29%; all
p < 0.05), suggesting that drugs were restricted
at effective doses to the spinal cord. We conclude that phrenic LTF
requires spinal serotonin receptor activation and protein synthesis.
Serotonin receptors on phrenic motoneuron dendrites may induce new
protein synthesis, thereby giving rise to phrenic LTF.
Key words:
control of breathing; serotonin; plasticity; intermittent
hypoxia; motoneuron; long-term facilitation
Copyright © 2002 Society for Neuroscience 0270-6474/02/22146239-08$05.00/0
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