Hypercapnia-induced activation of brainstem GABAergic neurons during early development

• Published in: Respiratory physiology & neurobiology 2003-06, Vol.136 (1), p.25-37
• Main Authors: Zhang, L., Wilson, C.G., Liu, S., Haxhiu, M.A., Martin, R.J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Biological and medical sciences; Brain Stem - growth & development; Brain Stem - pathology; c-Fos; Carbon dioxide; Carbon Dioxide - pharmacology; Cell Count; Control of breathing; Development; Fundamental and applied biological sciences. Psychology; GABA; GABAergic mechanisms; gamma-Aminobutyric Acid - metabolism; Gene; Hypercapnia - physiopathology; Immunohistochemistry - methods; Mammals; Neurons - metabolism; Parvalbumins - metabolism; Pattern of breathing; piglet; Proto-Oncogene Proteins c-fos - metabolism; respiratory timing; Swine
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/S1569-9048(03)00041-7

During early development, GABAergic mechanisms contribute to the regulation of respiratory timing in response to CO 2. In 5–7 day old piglets, a double labeling technique was used to determine whether GABA-containing neurons are activated by normoxic hypercapnia (10% CO 2, 21% O 2, and 69% N 2). The c-Fos gene encoded protein (c-Fos) was employed to localize CO 2 activated cells within the piglet medulla oblongata. Parvalbumin was used as a marker for GABAergic neurons. In animals breathing room air, only scant c-Fos-like immunoreactive neurons were observed. A marked increase in c-Fos positive cells was induced after a 60 min exposure to hypercapnia. Colocalization studies revealed that hypercapnia significantly increased c-Fos expression in GABA-containing neurons in the medulla oblongata, especially in the ventral aspect of the medulla, within the Bötzinger region, the gigantocellular reticular nucleus, and the caudal raphe nuclei. Only a few double-labeled cells were observed within the nucleus tractus solitarius. Therefore, brainstem GABAergic neurons are part of the neural networks that respond to CO 2 and may contribute to respiratory frequency responses to hypercapnia during early development.