The effects of hypothalamic peptides vasopressin and oxytocin on breathing via interaction with the retrotrapezoid nucleus

Abstract

The respiratory parafacial region, which encompasses the retrotrapezoid nucleus,(pFRG/RTN) modulates breathing to maintain arterial CO 2 levels and blood pH, significantly adjusting respiration during sleep and exercise. The paraventricular nucleusof the hypothalamus (PVN) is involved in several homeostatic processes includingmaintenance of metabolic, autonomic, and respiratory function. More than 30 distinctneuromodulators are synthesized by PVN neurons; most abundantly are vasopressin (VP)and oxytocin (OX), however, despite PVN projections to the pFRG/RTN, the roles of VPand OX in regulation of RTN function are largely unknown. To address this question, weevaluate whether oxytocinergic and vasopressinergic signaling influences the activity ofRTN neurons in vitro and whether oxytocin can induce changes in breathing in vivo. Maleor female C57B6/J, Phox2b::Cre;Ai14 or Oxt::Cre;Ai32 mice [P7-11 (neonate) or P100(adult)] were used (CEUA-ICB/USP: nº 9750170720). At the cellular level, cell-attachedrecordings from RTN neurons show that exposure to the vasopressin agonist (Arg8-Vasopressin or VP: 25 nM) increased firing rate from 1.2 ± 1.2 Hz to 3.5 ± 1.2. Thisresponse was decreased by 44% in the presence of fast neurotransmitter receptor blockers.Similarly, exogenous application of the OX agonist (TGOT: 2 nM) increased activity ofRTN neurons by 1.8 ± 0.5 Hz under control conditions and 2 ± 0.8 Hz in the presence ofthe synaptic blocker cocktail. In vivo experiments demonstrate that TGOT (1 µM - 30nL) injection or optogenetic stimulation of oxytocinergic terminals in the RTN regionincreased intercostal electromyography (IntEMG) amplitude (16.3 ± 10.9% vs. saline: 2.7± 4.2%, and optogenetic stimulation: 18.7 ± 8.3% of baseline), but without changingIntEMG frequency. Our findings indicate that VP and OX signaling exerts an excitatoryeffect within the RTN neurons, and that oxytocin plays a significant role in modulatingrespiratory activity through interactions in this region. FAPESP, CNPq, CAPES-PROEX This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.