title: Orexin A activates retrotrapezoid neurons in mice.
abstract: The retrotrapezoid nucleus (RTN), located at the ventral surface of the medulla oblongata, contains glutamatergic Phox2b-expressing interneurons that have central respiratory chemoreceptor properties. RTN also operates as a relay for hypothalamic pathways that regulate breathing, one of which probably originates from the orexinergic neurons (Dias et al., 2009. J. Physiol. 587, 2059-2067). The present study explores this hypothesis at the cellular level. Using immunohistochemistry in adult Phox2b-eGFP transgenic mice, we demonstrate the presence of numerous close appositions between orexin-containing axonal varicosities and RTN chemoreceptor neurons. Using electrophysiological recordings in slices from neonatal (P6-P10) Phox2b-eGFP mice, we show that orexin A produces a robust dose-dependent excitation of the acid-sensitive RTN neurons (ED(50) ∼250nM). These data support the idea that RTN neurons are a point of convergence for several groups of CNS neurons that contribute to respiratory chemoreflexes, now including serotonergic and orexinergic neurons.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, United States.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Lazarenko
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Stornetta
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bayliss
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000502:physiology; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D000068797:Orexins; D012119:Respiration; D012125:Respiratory Center / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C109220:NBPhox protein; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D014157:Transcription Factors