Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term facilitation of phrenic nerve activity; central chemoreceptor stimulation does not. The network mechanisms through which each class of chemoreceptor differentially influences breathing are poorly understood. Microelectrode arrays were used to monitor sets of spike trains from 114 PRG, 198 VRC and 166 midline neurons in six decerebrate vagotomized cats; 356 were recorded during sequential stimulation of both receptor classes via brief CO 2 -saturated saline injections in vertebral (central) and carotid arteries (peripheral). Seventy neurons responded to both stimuli. More neurons were responsive only to peripheral challenges than those responsive only to central chemoreceptor stimulation (PRG, 20 : 4; VRC, 41 : 10; midline, 25 : 13). Of 16 474 pairs of neurons evaluated for short-time scale correlations, similar percentages of reference neurons in each brain region had correlation features indicative of a specific interaction with at least one target neuron: PRG (59.6%), VRC (51.0%) and raphé nuclei (45.8%). The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor-mediated influences on breathing.

Download Full-text

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00222.2005 ◽

2005 ◽

Vol 289 (3) ◽

pp. R789-R797 ◽

Cited By ~ 64

Author(s):

Maram K. Reddy ◽

Kaushik P. Patel ◽

Harold D. Schultz

Keyword(s):

Paraventricular Nucleus ◽

Potassium Cyanide ◽

Reflex Response ◽

Nerve Activity ◽

Peripheral Chemoreceptor ◽

Peripheral Chemoreceptors ◽

Arterial Blood ◽

Central Chemoreceptors ◽

Stimulation Of

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 μg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO2). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated ( P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation ( P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses ( P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.

Download Full-text

Electrical Stimulation of the Raphe Nuclei: Effects on Runway Performance

PsycEXTRA Dataset ◽

10.1037/e463442008-120 ◽

1969 ◽

Author(s):

H. B. Van Twyver ◽

M. D. Fairchild ◽

M. B. Sterman

Keyword(s):

Electrical Stimulation ◽

Raphe Nuclei ◽

Runway Performance ◽

Raphé Nuclei ◽

Stimulation Of

Download Full-text

Stimulation of the raphe nuclei produces EEG spikes in the hippocampus of the normal rabbit.

Journal of Nippon Medical School ◽

10.1272/jnms1923.51.557 ◽

1984 ◽

Vol 51 (5) ◽

pp. 557-567

Author(s):

Shiro Minami

Keyword(s):

Raphe Nuclei ◽

Raphé Nuclei ◽

Stimulation Of

Download Full-text

Quipazine Elicits Swallowing in the Arterially Perfused Rat Preparation: A Role for Medullary Raphe Nuclei?

International Journal of Molecular Sciences ◽

10.3390/ijms21145120 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5120

Author(s):

Victor Bergé-Laval ◽

Christian Gestreau

Keyword(s):

Therapeutic Option ◽

Experimental Studies ◽

Raphe Nuclei ◽

Excitatory Effect ◽

Motor Patterns ◽

Systemic Injection ◽

Medullary Raphe ◽

Raphé Nuclei ◽

Stimulation Of

Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working heart-brainstem (in situ) preparation in rats. Systemic injection of quipazine produced single swallows with motor patterns and swallow-breathing coordination similar to spontaneous swallows, and increased swallow rate with moderate changes in cardiorespiratory functions. Methysergide, a 5-HT2 receptor antagonist, blocked the excitatory effect of quipazine on swallowing, but had no effect on spontaneous swallow rate. Microinjections of quipazine in the nucleus of the solitary tract were without effect. In contrast, similar injections in caudal medullary raphe nuclei increased swallow rate without changes in cardiorespiratory parameters. Thus, quipazine may exert an excitatory effect on raphe neurons via stimulation of 5-HT2A receptors, leading to increased excitability of the swallowing network. In conclusion, we suggest that pharmacological stimulation of swallowing by quipazine in situ represents a valuable model for experimental studies. This work paves the way for future investigations on brainstem serotonergic modulation, and further identification of neural populations and mechanisms involved in swallowing and/or swallow-breathing interaction.

Download Full-text

Role of central and peripheral chemoreceptors in diving responses of ducks

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.243.5.r537 ◽

1982 ◽

Vol 243 (5) ◽

pp. R537-R545 ◽

Cited By ~ 2

Author(s):

D. R. Jones ◽

W. K. Milsom ◽

G. R. Gabbott

Keyword(s):

Carotid Body ◽

Significant Contribution ◽

Cardiovascular Responses ◽

Peripheral Circulation ◽

Blood Gas ◽

Peripheral Chemoreceptors ◽

Central Chemoreceptors ◽

The Right ◽

Stimulation Of

Using techniques of vascular isolation and subsequent perfusion we have investigated the effects of altering blood gas tensions, in the cerebral and carotid body circulations, on some cardiovascular responses to diving in unanesthetized ducks. After denervating the right carotid body, perfusion of the innervated left carotid body with hyperoxic blood significantly reduced diving bradycardia and reduced the increase in hindlimb vascular resistance (HLVR) in 1-min dives compared with dives in which the innervated carotid body was autoperfused. Denervation of systemic arterial baroreceptors reduced the fall in heart rate (HR) and increased the rise in HLVR in all dives. Cross-perfusion of the head, from a donor with blood of normal blood gas tensions, did not significantly affect HR or HLVR in 2-min dives compared with dives in which the head was autoperfused. however, cross-perfusing the cerebral circulation with blood of elevated PaCO2 caused significantly greater increases in HLVR than when high PaCO2 only affected the peripheral circulation. We conclude that peripheral chemoreceptors cause virtually all the bradycardia in the later stages of a dive but only about one-half the increase in HLVR, a significant contribution comes from the stimulation of central chemoreceptors with blood of high PaCO2.

Download Full-text

Stimulation of the rat medullary raphe nuclei induces differential responses in respiratory muscle activity

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2008.12.004 ◽

2009 ◽

Vol 165 (2-3) ◽

pp. 208-214 ◽

Cited By ~ 13

Author(s):

S. Besnard ◽

P. Denise ◽

B. Cappelin ◽

M. Dutschmann ◽

C. Gestreau

Keyword(s):

Muscle Activity ◽

Respiratory Muscle ◽

Raphe Nuclei ◽

Medullary Raphe ◽

Differential Responses ◽

Raphé Nuclei ◽

Respiratory Muscle Activity ◽

Stimulation Of

Download Full-text

Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00317.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. G341-G348 ◽

Cited By ~ 5

Author(s):

Hiroyuki Nakamori ◽

Kiyotada Naitou ◽

Yuuki Horii ◽

Hiroki Shimaoka ◽

Kazuhiro Horii ◽

...

Keyword(s):

Spinal Cord ◽

Electrical Stimulation ◽

Raphe Nuclei ◽

Lumbosacral Spinal Cord ◽

Pelvic Nerves ◽

Medullary Raphe ◽

Raphé Nuclei ◽

Type 3 ◽

Stimulation Of

Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.

Download Full-text