Paraventricular oxytocin neurons are involved in neural modulation of breathing

Abstract

In this study, we determined the projections of oxytocin-containing neurons of the paraventricular nucleus (PVN) to phrenic nuclei and to the rostral ventrolateral medullary (RVLM) region, which is known to be involved in respiratory rhythm generation. Studies were also designed to determine oxytocin-receptor expression within the RVLM and the physiological effects of their activation on respiratory drive and arterial blood pressure. Oxytocin immunohistochemistry combined with cholera toxin B, a retrograde tracer, showed that a subpopulation of oxytocin-containing parvocellular neurons in the dorsal and medial ventral regions of the PVN projects to phrenic nuclei. Similarly, a subpopulation of pseudorabies virus-labeled neurons in the PVN coexpressed oxytocin after injection of pseudorabies virus, a transynaptic retrograde marker, into the costal region of the diaphragm. A subpopulation of oxytocin expressing neurons was also found to project to the RVLM. Activation of this site by microinjection of oxytocin into the RVLM (0.2 nmol/200 nl) significantly increased diaphragm electromyographic activity and frequency discharge (P < 0.05). In addition, oxytocin increased blood pressure and heart rate (P < 0.05). These data indicate that oxytocin participates in the regulation of respiratory and cardiovascular activity, partly via projections to the RVLM and phrenic nuclei.

Water deprivation activates a glutamatergic projection from the hypothalamic paraventricular nucleus to the rostral ventrolateral medulla

“…We found a few OT-NP-ir PVH neurons with projections to RVLM (2.2% of CTB-labeled neurons in PVH). This figure closely matches the percentage of oxytocin neurons projecting to the caudal ventrolateral medulla (3.3%) reported by Mack et al (2002). Hancock and Nicholas (1987) also reported an oxytocinergic innervation of the ventrolateral medulla using immunohistochemical labeling of oxytocin fibers making close contacts with PNMTir neurons.…”

“…According to several studies, these peptidergic PVH neurons project to the spinal cord and/or to the dorsomedial medulla (Nilaver et al, 1980;Sawchenko and Swanson, 1982;Hallbeck and Blomqvist, 1999;Hallbeck et al, 2001) or the ventrolateral medulla (Hancock and Nicholas, 1987;Gomez et al, 1993;Mack et al, 2002). We found a few OT-NP-ir PVH neurons with projections to RVLM (2.2% of CTB-labeled neurons in PVH).…”

“…Previous reports suggest that some parvocellular PVH neurons with descending projections to the hindbrain may be oxytocinergic or vasopressinergic (Sawchenko and Swanson, 1982;Hallbeck and Blomqvist, 1999;Hallbeck et al, 2001;Mack et al, 2002;Kc et al, 2002). In this regard, microinjection of vasopressin or oxytocin into the RVLM increases arterial blood pressure (Andreatta-Van Leyen et al, 1990;Gomez et al, 1993;Mack et al, 2002;Kc et al, 2002) and vasopressin-and oxytocin-immunoreactive fibers have been found in close proximity to spinally-projecting RVLM neurons (Hancock and Nicholas, 1987;Gomez et al, 1993). Moreover, blockade of vasopressin-type 1 receptors attenuates PVH-evoked increases in RVLM unit discharge (Yang et al, 2001;Yang and Coote, 2003).…”

Pituitary adenylate cyclase-activating polypeptide maintains neonatal breathing but not metabolism during mild reductions in ambient temperature

“…It is equally possible that PACAP maintains V E by stimulating neurons that are activated by reductions in ambient and/or body temperature but do not participate directly in the chemoreflexes. We note that neurons within the preoptic and paraventricular nuclei of the hypothalamus that are involved in temperature regulation also project to and stimulate phrenic motoneurons (6,19,24,25) and receive dense innervation from PACAP-positive axons (2,9,34). Finally, it is also possible that the effect of PACAP on the ventilatory responses to cooling are indirect, being mediated by other neuropeptides or hormones.…”

Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure

“…In addition, Yeh and coworkers (27) reported direct connections between the PVN and phrenic motoneurons. Later, Mack and colleagues (9) demonstrated that oxytocin neurons in the PVN were involved in neuronal modulation of breathing by projecting to the RVLM pre-Bötzinger complex neurons and the phrenic motorneurons. Probably these connections to respiratory centers, and autonomic regions involved in regulation of sympathetic and cardiovascular functions, would provide the PVN with mechanism, which could potentially influence the sympathetic and cardiorespiratory responses during the activation of CB chemoreceptors.…”