Identification of a novel form of noradrenergic-dependent respiratory motor plasticity triggered by vagal feedback

J Neurosci. 2010 Dec 15;30(50):16886-95. doi: 10.1523/JNEUROSCI.3394-10.2010.


The respiratory control system is not just reflexive, it is smart, it learns, and, in fact, it has a memory. The respiratory system listens to and carefully remembers how previous stimuli affect breathing. Respiratory memory is laid down by adjusting synaptic strength between respiratory neurons. For example, repeated hypoxic bouts trigger a form of respiratory memory that functions to strengthen the ability of respiratory motoneurons to trigger contraction of breathing muscles. This type of respiratory plasticity is known as long-term facilitation (LTF). Although chemical feedback, such as hypoxia, initiates LTF, it is unknown whether natural modulation of mechanical feedback (from vagal inputs) also causes motor plasticity. Here, we used reverse microdialysis, electrophysiology, neuropharmacology, and histology to determine whether episodic modulation of vagally mediated mechanical feedback is able to induce respiratory LTF in anesthetized adult rats. We show that repeated obstructive apneas disrupt vagal feedback and trigger LTF of hypoglossal motoneuron activity and genioglossus muscle tone. This same stimulus does not cause LTF of diaphragm activity. Hypoxic episodes do not cause apnea-induced LTF; instead, LTF is triggered by modulation of vagal feedback. Unlike hypoxia-induced respiratory plasticity, vagus-induced LTF does not require 5-HT(2) receptors but instead relies on activation of α1-adrenergic receptors on hypoglossal motoneurons. In summary, we identify a novel form of hypoxia- and 5-HT-independent respiratory motor plasticity that is triggered by physiological modulation of vagal feedback and is mediated by α1-adrenergic receptor activation on (or near) hypoglossal motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Apnea / physiopathology
  • Diaphragm / physiology
  • Feedback, Sensory / physiology*
  • Hypoglossal Nerve / drug effects
  • Hypoxia
  • Ketanserin / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Motor Neurons / physiology*
  • Prazosin / analogs & derivatives
  • Prazosin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / physiology
  • Receptors, AMPA / agonists
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Respiratory System / innervation*
  • Serotonin Antagonists / pharmacology
  • Vagus Nerve / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Adrenergic alpha-1 Receptor Antagonists
  • Receptor, Serotonin, 5-HT2A
  • Receptors, AMPA
  • Receptors, Adrenergic, alpha-1
  • Serotonin Antagonists
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Terazosin
  • Ketanserin
  • Prazosin