Blockade of dorsolateral pontine 5HT1A receptors destabilizes the respiratory rhythm in C57BL6/J wild-type mice

Respir Physiol Neurobiol. 2016 Jun:226:110-4. doi: 10.1016/j.resp.2016.01.007. Epub 2016 Feb 1.

Abstract

The neurotransmitter serotonin (5HT) acting via 5HT1a receptors (5HT1aR) is a potent determinant of respiratory rhythm variability. Here, we address the 5HT1aR-dependent control of respiratory rhythm variability in C57BL6/J mice. Using the in situ perfused preparation, we compared the effects of systemic versus focal blockade of 5HT1aRs. Blocking 5HT1aRs in the Kölliker-Fuse nucleus (KFn) increased the occurrence of spontaneous apneas and accounted for the systemic effects of 5HT1aR antagonists. Further, 5HT1aRs of the KFn stabilized the respiratory rhythm's response to arterial chemoreflex perturbations; reducing the recovering time, e.g., the latency to return to the baseline pattern. Together, these results suggest that the KFn regulates both intrinsic and sensory determinants of respiratory rhythm variability.

Keywords: Control of breathing; Gain control; Kölliker-Fuse nuclei (KFN); Mecp2-deficient mice; Rett Syndrome; Serotonin (5-HT); Variability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apnea / chemically induced
  • Apnea / metabolism
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / physiology
  • Cyclohexanes / pharmacology*
  • Female
  • Kolliker-Fuse Nucleus / drug effects*
  • Kolliker-Fuse Nucleus / metabolism*
  • Membrane Potentials / drug effects
  • Mice, 129 Strain
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peripheral Nervous System Agents / pharmacology
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / physiology
  • Piperazines / pharmacology*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Reflex / drug effects
  • Reflex / physiology
  • Respiration / drug effects*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology*
  • Sodium Cyanide / pharmacology
  • Tissue Culture Techniques

Substances

  • Cyclohexanes
  • Peripheral Nervous System Agents
  • Piperazines
  • Serotonin 5-HT1 Receptor Antagonists
  • WAY 101363
  • Receptor, Serotonin, 5-HT1A
  • Sodium Cyanide