PVN neuropeptide neurons may modulate nTS activation and cardiorespiratory responses to peripheral chemoreflex stimulation

The paraventricular nucleus of the hypothalamus (PVN) is required for full expression of cardiorespiratory responses evoked by peripheral chemoreflex stimulation, but the efferent pathways have not been fully elucidated. We previously reported that hypoxia activates (Fos‐immunoreactivity; IR) PVN neurons that project to the nucleus tractus solitarii (nTS). The majority of hypoxia‐activated nTS‐projecting neurons are CRH‐IR. These findings suggest that the PVN may influence chemoreflex‐evoked cardiorespiratory function via CRH actions in the nTS. CRFR2 is the predominant CRH receptor in the nTS. Previous studies indicate that selective activation of nTS CRFR2s produces cardiovascular responses consistent with excitation. CRFR2 co‐localizes extensively with oxytocin‐IR fibers, likely from the PVN, and nTS oxytocin enhances baroreflex function. We hypothesized that interactions between PVN neuropeptide neurons, including CRH binding to CRFR2s located on oxytocin fibers, modulates nTS neuronal activation and thus may augment cardiorespiratory responses to peripheral chemoreflex stimulation. An AAV viral vector expressing mCherry under the CAMKII promoter was injected into the PVN, and mCherry‐expressing fibers were evaluated in the nTS. Immunohistochemical evaluation revealed that mCherry‐expressing fibers formed close appositions with nTS neurons (indicated by HUC/D‐IR), including neurons activated by acute hypoxia (2 hr 10% O 2 ). These findings suggest that PVN inputs to the nTS may modulate the activation of nTS neurons that respond to hypoxia. A separate group of animals received bilateral injections of the retrograde tracer CTB into either the PVN or the RVLM. Immunohistochemistry examined the extent to which CRFR2 fibers contact CTB‐labeled neurons in the nTS. CRFR2 fibers made close appositions with specific populations of nTS neurons activated by acute hypoxia, including catecholaminergic (tyrosine hydroxylase, TH‐IR), RVLM‐projecting and PVN‐projecting cells. Together, these data suggest that PVN neuropeptide projections to the nTS may modulate the activation of subpopulations of nTS neurons in response to hypoxia. We suggest that PVN neuropeptide neurons projecting to the nTS may shape the cardiorespiratory responses evoked by peripheral chemoreflex stimulation. Future in vivo experiments will determine the physiological relevance of PVN neuropeptide projections to the nTS, including the extent to which nTS CRH and/or oxytocin influence basal and chemoreflex‐evoked cardiorespiratory output. Support or Funding Information NIH RO1 HL98602