Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

Abstract

Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60-90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P< 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.

Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

“…We have shown that hypoxia produces significant activation of PVN-projecting catecholaminergic neurons in both nTS and VLM, particularly at greater hypoxia intensities (24,26). However, the function of these projections was not determined.…”

“…Catecholamine neurons projecting to the PVN are activated by cardiovascular challenges, including hypovolemia and osmotic stimuli (12,24,26). However, PVN involvement in cardiovascular adaptations specifically to hypoxia has not been evaluated thoroughly.…”

“…These catecholaminergic populations respond and contribute to responses to a variety of cardiorespiratory stimuli (7,22,24,48). For example, A1 noradrenergic neurons in the caudal VLM (CVLM) are activated by hypoxia (26,55), and CVLM lesion attenuates vasopressin and corticotropin-releasing hormone (CRH) responses to hypoxia (55). Furthermore, PVN adrenergic blockade blunts cardiovascular and vasopressin responses to acute chemoreflex stimulation in spinally transected rats (32).…”

“…Importantly, a large proportion of these projection neurons is catecholaminergic (24,26). However, the extent to which catecholaminergic input to the PVN plays a functional role in cardiorespiratory responses to acute hypoxia is unknown.…”

Regulation of the chemosensory control of breathing by Kölliker-Fuse neurons

“…It is interesting to note that our hypoxia protocol elicited a reduction in arterial pressure. Acute hypoxia in conscious rats produces a moderate depressor response (31,32). In addition, LPB cells receive convergent baroreceptor and chemoreceptor inputs (27,52), and LPB neurons respond to decreases in arterial pressure (37).…”