Activation of a latent respiratory motor pathway by stimulation of neurons in the medullary chemoreceptor area of the rat.
Previous studies have demonstrated that during respiratory stress (hypercapnia and hypoxia), a latent crossed respiratory pathway can be activated to produce hemidiaphragm recovery following an ipsilateral C2 spinal cord hemisection. The present study investigates the effects of ventral medullary chemoreceptor area stimulation by microinjection of (1S,3R)-aminocyclopentanedicarboxylic acid (ACPD), a glutamate metabotropic receptor agonist, on activating the latent pathway following left C2 spinal cord hemisection in rats in which end-tidal CO2 was maintained at a constant level. Experiments were conducted on anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which phrenic nerve activity was recorded bilaterally. Before drug injection, the phrenic nerve contralateral to hemisection showed vigorous respiratory-related activity, but the phrenic nerve ipsilateral to hemisection showed no discernible respiratory-related activity. ACPD (1-100 nl, 1 mM) was injected directly into the region of the retrotrapezoid nucleus (RTN), a known medullary chemoreceptor area. Microinjection of ACPD into the right RTN increased respiratory-related activity in the right phrenic nerve (contralateral to hemisection). ACPD (>5 nl, 1 mM) microinjection also significantly induced respiratory recovery in the phrenic nerve ipsilateral to hemisection in a dose-dependent manner. The present study indicates that respiratory recovery can be achieved by stimulation of respiratory circuitry without increasing CO2 levels.
Zhou
S Y
SY
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 East Canfield, Detroit, Michigan 48201, USA.
Castro-Moure
F
F
Goshgarian
H G
HG
D000818:Animals; D002245:Carbon Dioxide / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011659:Pulmonary Gas Exchange; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D020127:Recovery of Function / Q000187:drug effects; D012121:Respiration, Artificial; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology; D013268:Stimulation, Chemical; D013990:Tidal Volume / Q000502:physiology; D014628:Vagotomy
D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002245:Carbon Dioxide