Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

• Published in: Pflügers Archiv Vol. 462; no. 3; pp. 407 - 418
• Main Authors: da Silva, Glauber S. F., Giusti, Humberto, Benedetti, Maurício, Dias, Mirela B., Gargaglioni, Luciane H., Branco, Luiz Guilherme S., Glass, Mogens L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-09-2011; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blood; Carbon Dioxide - blood; Carotid Body - cytology; Carotid Body - physiology; Cell Biology; Chemoreceptor Cells - physiology; Human Physiology; Hypercapnia - metabolism; Integrative Physiology; Male; Molecular Medicine; Neurosciences; Oxygen - blood; Pulmonary Ventilation - physiology; Raphe Nuclei - cytology; Raphe Nuclei - pathology; Rats; Rats, Wistar; Receptors; Respiration; Serotonergic Neurons - cytology; Serotonergic Neurons - metabolism; Serotonergic Neurons - pathology; Hypercapnia; Central chemoreception; Pulmonary ventilation; Peripheral chemoreception; 5-HT neurons; Medullary raphe
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-011-0990-x

Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in the respiratory control network. However, it is not known whether ROb 5-HT neurons play a role in the functional interdependence between central and peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT neurons in the ventilatory responses to CO
2
and their putative involvement in the central–peripheral CO
2
chemoreceptor interaction in unanaesthetised rats. We used a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (
V
E
), body temperature and the arterial blood gases were measured before, during and after a hypercapnic challenge (7% CO
2
). The lesion of ROb 5-HT neurons alone (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline
V
E
during normocapnic condition. Killing ROb 5-HT neurons (CB intact) significantly decreased the ventilatory response to hypercapnia (
p
 < 0.05). The reduction in CO
2
sensitivity was approximately 15%. When ROb 5-HT neurons lesion was combined with CBR (anti-SERT-SAP+CBR), the
V
E
response to hypercapnia was further decreased (−31.2%) compared to the control group. The attenuation of CO
2
sensitivity was approximately 30%, and it was more pronounced than the sum of the individual effects of central (ROb lesion; −12.3%) or peripheral (CBR; −5.5%) treatments. Our data indicate that ROb 5-HT neurons play an important role in the CO
2
drive to breathing and may act as an important element in the central–peripheral chemoreception interaction to CO
2
responsiveness.