Respiratory Research

, 2:3.1 | Cite as

Serotonin-dependent respiratory plasticity

  • GS Mitchell
  • TL Baker
  • DD Fuller
  • RW Bavis
Open Access
ORAL PRESENTATIONS - SESSION 3
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Keywords

Brain Derive Neurotrophic Factor Serotonin Receptor Methysergide Emetine Episodic Hypoxia 

Serotonin initiates neuroplasticity in a number of invertebrate and vertebrate experimental models. The first report of serotonin-dependent plasticity in respiratory motor control was a long-lasting facilitation of phrenic activity following episodic stimulation of chemoafferent neurons [1], a phenomenon now known as long-term facilitation (LTF). Recent progress has contributed considerably towards an understanding of the mechanisms and manifestations of this potentially important model of respiratory plasticity. In this presentation, recent progress in understanding the mechanism of LTF will be reviewed. In all studies, we exposed awake or anesthetized Sprague Dawley rats to episodic hypoxia as an experimental model of LTF. Both awake and anesthetized rats express LTF following episodic hypoxia. Intermittent, but not continuous hypoxia elicits LTF, indicating remarkable pattern sensitivity in its underlying mechanism. Both episodic chemoafferent activation by stimulation of the carotid sinus nerve and episodic hypoxia in carotid denervated rats elicit LTF, suggesting that at least two discrete mechanisms contribute to LTF in anesthetized rats. Hypoxia-induced LTF requires serotonin receptor activation during, but not following episodic hypoxia, indicating that serotonin is necessary to initiate but not maintain LTF. Phrenic LTF following episodic hypoxia is blocked by intrathecal administration of a serotonin receptor antagonist (methysergide) or protein synthesis inhibitors (cyclohexamide, emetine) to the cervical spinal cord. On the other hand, intraspinal drug administration had no effect on hypoglossal LTF. Thus, the relevant serotonin receptors in phrenic LTF are within the spinal cord, suggesting a location within the respiratory motor nucleus itself. These observations form the basis of our working hypothesis that LTF is initiated by episodic activation of 5-HT2 receptors on respiratory motoneurons, thereby initiating a cell-signaling cascade leading to new protein synthesis. Although the specific protein(s) necessary for LTF is (are) unknown, we recently found that episodic hypoxia and LTF are associated with elevations in ventral spinal concentrations of brain derived neurotrophic factor (BDNF). The elevation in BDNF following episodic hypoxia is blocked by local application of methysergide, suggesting that it may be a causal agent in LTF. Although the physiological (or pathophysiological) role of LTF is uncertain, it may reflect a general mechanism whereby intermittent activation of raphe serotonergic neurons elicits plasticity in respiratory motoneurons. Thus, the same fundamental mechanism may be operational in a number of physiological (eg. altitude or repetitive exercise) or pathophysiological (eg. lung disease or neural injury) states.

Notes

Acknowledgement

This work was supported by NIH HL 53319 and HL 65383.

References

  1. 1.
    Millhorn DE, Eldridge FL, Waldrop TG: Prolonged stimulation of respiration by a new central neural mechanism. Resp Physiol. 1980, 41: 87-103. 10.1016/0034-5687(80)90025-0.CrossRefGoogle Scholar

Copyright information

© BioMed Central Ltd 2001

Authors and Affiliations

  • GS Mitchell
    • 1
  • TL Baker
    • 1
  • DD Fuller
    • 1
  • RW Bavis
    • 1
  1. 1.Departments of Comparative BiosciencesUniversity of WisconsinMadisonUSA

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