Stimulation of the midbrain periaqueductal gray modulates preinspiratory neurons in the ventrolateral medulla in the rat in vivo

J Comp Neurol. 2013 Sep 1;521(13):3083-98. doi: 10.1002/cne.23334.


The midbrain periaqueductal gray (PAG) is involved in many basic survival behaviors that affect respiration. We hypothesized that the PAG promotes these behaviors by changing the firing of preinspiratory (pre-I) neurons in the pre-Bötzinger complex, a cell group thought to be important in generating respiratory rhythm. We tested this hypothesis by recording single unit activity of pre-Bötzinger pre-I neurons during stimulation in different parts of the PAG. Stimulation in the dorsal PAG increased the firing of pre-I neurons, resulting in tachypnea. Stimulation in the medial part of the lateral PAG converted the pre-I neurons into inspiratory phase-spanning cells, resulting in inspiratory apneusis. Stimulation in the lateral part of the lateral PAG generated an early onset of the pre-I neuronal discharge, which continued throughout the inspiratory phase, while at the same time attenuating diaphragm contraction. Stimulation in the ventral part of the lateral PAG induced tachypnea but inhibited pre-I cell firing, whereas stimulation in the ventrolateral PAG inhibited not only pre-I cells but also the diaphragm, leading to apnea. These findings show that PAG stimulation changes the activity of the pre-Bötzinger pre-I neurons. These changes are in line with the different behaviors generated by the PAG, such as the dorsal PAG generating avoidance behavior, the lateral PAG generating fight and flight, and the ventrolateral PAG generating freezing and immobility.

Keywords: inspiration; periaqueductal gray; pre-Bötzinger; pre-I neuron; respiration; emotional behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Analysis of Variance
  • Animals
  • Electromyography
  • Fourier Analysis
  • Functional Laterality
  • Homocysteine / analogs & derivatives
  • Homocysteine / pharmacology
  • Male
  • Medulla Oblongata / cytology*
  • Medulla Oblongata / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Periaqueductal Gray / cytology
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Respiration*


  • Homocysteine
  • homocysteic acid