scholarly journals Hypoxia activates nucleus tractus solitarii neurons projecting to the paraventricular nucleus of the hypothalamus

2012 ◽  
Vol 302 (10) ◽  
pp. R1219-R1232 ◽  
Author(s):  
T. Luise King ◽  
Cheryl M. Heesch ◽  
Catharine G. Clark ◽  
David D. Kline ◽  
Eileen M. Hasser

Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia ( n = 4, 21% O2) or acute hypoxia (12, 10, or 8% O2; n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O2was similar whether arterial pressure was allowed to decrease (−13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O2. Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.

2017 ◽  
Vol 312 (6) ◽  
pp. R982-R995 ◽  
Author(s):  
K. Max Coldren ◽  
De-Pei Li ◽  
David D. Kline ◽  
Eileen M. Hasser ◽  
Cheryl M. Heesch

Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of AVP, corticotropin-releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brain stem pathway, including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS) neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR) cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR (~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and an excitatory role of NO on CRH secretion in the PVN and median eminence.


2013 ◽  
Vol 305 (10) ◽  
pp. R1112-R1123 ◽  
Author(s):  
T. Luise King ◽  
David D. Kline ◽  
Brian C. Ruyle ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser

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.


1998 ◽  
Vol 274 (5) ◽  
pp. R1345-R1352 ◽  
Author(s):  
R. R. Randolph ◽  
Q. Li ◽  
K. S. Curtis ◽  
M. J. Sullivan ◽  
J. T. Cunningham

Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation ( P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.


1984 ◽  
Vol 246 (6) ◽  
pp. R968-R978 ◽  
Author(s):  
J. Ciriello ◽  
M. M. Caverson

Horseradish peroxidase (HRP) and single-unit recording experiments were done in cats to identify neurons in ventrolateral medulla (VLM) that project directly to the paraventricular nucleus (PVH) and relay cardiovascular information from carotid sinus (CSN) and aortic depressor (ADN) nerves. After diffusion of HRP into the PVH, retrogradely labeled neurons were observed in the VLM. The region of the VLM containing HRP-labeled neurons was then explored for single units antidromically activated by stimulation of the PVH in chloralosed, paralyzed, and artificially ventilated cats. These units were then tested for their responses to stimulation of the CSN and ADN. Antidromic potentials were recorded from 100 units in the VLM. Of these units, 65% were orthodromically excited by stimulation of buffer nerves; 28 by only CSN, 19 by only ADN, and 18 by both CSN and ADN. The axons of antidromically activated units responding to buffer nerves conducted at slower velocities than those of nonresponsive units. These data demonstrate that VLM neurons projecting directly to PVH integrate cardiovascular afferent information and suggest that these VLM neurons may be involved in the control of the activity of magnocellular neurosecretory neurons in the PVH during activation of baroreceptor and chemoreceptor afferent fibers.


1998 ◽  
Vol 17 (3) ◽  
pp. 133-139 ◽  
Author(s):  
Xiao-Hui Xing ◽  
Ling Wang ◽  
Zhi-Ren Rao ◽  
Jing-Zao Chen

To clarify the effects of infrasound on the medulla, catecholaminergic neurons in the medulla expressing Fos were investigated in the rats by immunohistochemical method. After exposure to infrasound (8Hz, 120dB) for 2 hours, animals were sacrificed and sections of the medulla were stained immunohistochemically for Fos and tyrosine hydroxylase (TH). Many Fos-like immunoreactive neurons were found in the nucleus tractus solitarii (NTS) and Ventrolateral medulla (VLM) at the middle and caudal levels of medulla, only a few of them scattered in the reticular formation between NTS and VLM. Some Fos immunoreactive neurons were also labeled with TH. These results indicated that medulla was sensitive to infrasonic stimulation and some medullary catecholaminergic neurons might be involved in the responses to the stress produced by infrasound.


Sign in / Sign up

Export Citation Format

Share Document