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PMID: 16455687 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2-sensitive neurons in rats.

The Journal of physiology ·Vol. 572 ·No. Pt 2 ·2006-04-15 ·Pages 503-23

Takakura AC, Moreira TS, Colombari E, West GH, Stornetta RL, Guyenet PG

Abstract

The rat retrotrapezoid nucleus (RTN) contains pH-sensitive neurons that are putative central chemoreceptors. Here, we examined whether these neurons respond to peripheral chemoreceptor stimulation and whether the input is direct from the solitary tract nucleus (NTS) or indirect via the respiratory network. A dense neuronal projection from commissural NTS (commNTS) to RTN was revealed using the anterograde tracer biotinylated dextran amine (BDA). Within RTN, 51% of BDA-labelled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2) but only 5% contained glutamic acid decarboxylase-67 (GAD67). Awake rats were exposed to hypoxia (n = 6) or normoxia (n = 5) 1 week after injection of the retrograde tracer cholera toxin B (CTB) into RTN. Hypoxia-activated neurons were identified by the presence of Fos-immunoreactive nuclei. CommNTS neurons immunoreactive for both Fos and CTB were found only in hypoxia-treated rats. VGLUT2 mRNA was detected in 92 +/- 13% of these neurons whereas only 12 +/- 9% contained GAD67 mRNA. In urethane-chloralose-anaesthetized rats, bilateral inhibition of the RTN with muscimol eliminated the phrenic nerve discharge (PND) at rest, during hyperoxic hypercapnia (10% CO(2)), and during peripheral chemoreceptor stimulation (hypoxia and/or i.v. sodium cyanide, NaCN). RTN CO(2)-activated neurons were recorded extracellularly in anaesthetized intact or vagotomized rats. These neurons were strongly activated by hypoxia (10-15% O(2); 30 s) or by NaCN. Hypoxia and NaCN were ineffective in rats with carotid chemoreceptor denervation. Bilateral injection of muscimol into the ventral respiratory column 1.5 mm caudal to RTN eliminated PND and the respiratory modulation of RTN neurons. Muscimol did not change the threshold and sensitivity of RTN neurons to hyperoxic hypercapnia nor their activation by peripheral chemoreceptor stimulation. In conclusion, RTN neurons respond to brain P(CO(2)) presumably via their intrinsic chemosensitivity and to carotid chemoreceptor activation via a direct glutamatergic pathway from commNTS that bypasses the respiratory network. RTN neurons probably contribute a portion of the chemical drive to breathe.

MeSH Terms
Action Potentials Animals Biotin/analogs & derivatives,analysis,pharmacology Carbon Dioxide/pharmacology Carotid Body/physiology Chemoreceptor Cells/drug effects,physiology Cholera Toxin/analysis,pharmacology Dextrans/analysis,pharmacology Electrophysiology Excitatory Amino Acid Agents Glutamate Decarboxylase/analysis Glutamic Acid/analysis,physiology Hydrogen-Ion Concentration Hypercapnia/physiopathology Hypoxia/physiopathology Isoenzymes/analysis Male Medulla Oblongata/physiology Muscimol/pharmacology Neurons/chemistry,drug effects,physiology RNA, Messenger/analysis Rats Rats, Sprague-Dawley Respiratory Center/physiology Sodium Cyanide/pharmacology Vesicular Glutamate Transport Protein 2/analysis,genetics
Chemicals
Dextrans Excitatory Amino Acid Agents Isoenzymes RNA, Messenger Vesicular Glutamate Transport Protein 2 biotinylated dextran amine Carbon Dioxide Muscimol Glutamic Acid Biotin Cholera Toxin Glutamate Decarboxylase glutamate decarboxylase 1 Sodium Cyanide
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Takakura Ana Carolina Thomaz
Department of Pharmacology, University of Virginia Health System, Charlottesville, 22908-0735, USA.
Moreira Thiago Santos
Colombari Eduardo
West Gavin H
Stornetta Ruth L
Guyenet Patrice G
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2005.103788
Published
2006-04-15
Epub
2006-00-02
Pages
503-23
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1779666
Subset
IM
Grants
NHLBI NIH HHS · HL 74011 · United States
NHLBI NIH HHS · HL 28785 · United States
NHLBI NIH HHS · R01 HL028785 · United States
NHLBI NIH HHS · R01 HL074011 · United States
NHLBI NIH HHS · R37 HL028785 · United States
Corrections
CommentIn
PMID: 16484293
External Links
PubMed source DOI: 10.1113/jphysiol.2005.103788 PMC Full Text View journal details
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