title: Inhibition of the pontine Kölliker-Fuse nucleus reduces genioglossal activity elicited by stimulation of the retrotrapezoid chemoreceptor neurons.
abstract: The Kölliker-Fuse (KF) region, located in the dorsolateral pons, projects to several brainstem areas involved in respiratory regulation, including the chemoreceptor neurons within the retrotrapezoid nucleus (RTN). Several lines of evidence indicate that the pontine KF region plays an important role in the control of the upper airways for the maintenance of appropriate airflow to and from the lungs. Specifically, we hypothesized that the KF region is involved in mediating the response of the hypoglossal motor activity to central respiratory chemoreflex activation and to stimulation of the chemoreceptor neurons within the RTN region. To test this hypothesis, we combined immunohistochemistry and physiological experiments. We found that in the KF, the majority of biotinylated dextran amine (BDA)-labeled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2), but few contained glutamic acid decarboxylase-67 (GAD67). The majority of the RTN neurons that were FluorGold (FG)-immunoreactive (i.e., projected to the KF) contained hypercapnia-induced Fos, but did not express tyrosine hydroxylase. In urethane-anesthetized sino-aortic denervated and vagotomized male Wistar rats, hypercapnia (10% CO2) or N-methyl-d-aspartate (NMDA) injection (0.1mM) in the RTN increased diaphragm (DiaEMG) and genioglossus muscle (GGEMG) activities and elicited abdominal (AbdEMG) activity. Bilateral injection of muscimol (GABA-A agonist; 2mM) into the KF region reduced the increase in DiaEMG and GGEMG produced by hypercapnia or NMDA into the RTN. Our data suggest that activation of chemoreceptor neurons in the RTN produces a significant increase in the genioglossus muscle activity and the excitatory pathway is dependent on the neurons located in the dorsolateral pontine KF region.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil.
authors.forename: Josiane N
authors.initials: JN
authors.lastname: Silva
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil.
authors.forename: Elvis V
authors.initials: EV
authors.lastname: Lucena
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil.
authors.forename: Talita M
authors.initials: TM
authors.lastname: Silva
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil.
authors.forename: Rosélia S
authors.initials: RS
authors.lastname: Damasceno
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo (USP), 05508-000 São Paulo/SP, Brazil. Electronic address: tmoreira@icb.usp.br.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000166:cytology / Q000502:physiology*; D003964:Diaphragm / Q000294:innervation / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006935:Hypercapnia / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011149:Pons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D014059:Tongue / Q000294:innervation / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D009118:Muscimol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: breathing; chemoreflex; dorsolateral pons; genioglossal activity; ventrolateral medulla