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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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