Orexin A activates retrotrapezoid neurons in mice.

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.