title: CO2-inhibited neurons in the medullary raphé are GABAergic.
abstract: Previous studies have reported subsets of medullary raphé neurons that are either stimulated or inhibited by CO2/pH in vitro, in situ, and in vivo. We tested the hypothesis that medullary raphé CO2-inhibited neurons are GABAergic. Extracellular recordings in unanesthetized juvenile in situ rat preparations showed reversible hypercapnia-induced suppression of 19% (63/323) of medullary raphé neurons, and this suppression persisted after antagonism of NMDA, AMPA/kainate, and GABAA receptors. We stained a subset of CO2-inhibited cells and found that most (11/12) had glutamic acid decarboxylase 67 immunoreactivity (GAD67-ir). These data indicate that the majority of acidosis-inhibited medullary raphé neurons are GABAergic, and that their chemosensitivity is independent of major fast synaptic inputs. Thus, CO2-sensitive GABAergic neurons may play a role in central CO2/pH chemoreception.
authors.affiliation: Institute of Arctic Biology and Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Iceman
authors.affiliation: Institute of Arctic Biology and Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Corcoran
authors.affiliation: Institute of Arctic Biology and Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Taylor
authors.affiliation: Institute of Arctic Biology and Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Electronic address: mbharris@alaska.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Harris
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D066267:Midbrain Raphe Nuclei / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010879:Piperazines; D002245:Carbon Dioxide; D005680:gamma-Aminobutyric Acid; C093086:biotinamide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001710:Biotin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D014365:Tryptophan Hydroxylase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D001640:Bicuculline
keywords: Breathing; Chemosensitivity; GABA; Raphé
references.citation: J Appl Physiol (1985). 2007 Nov;103(5):1780-8
references.pmid: 17823301
references.citation: Am J Physiol Regul Integr Comp Physiol. 2012 Mar 1;302(5):R551-60
references.pmid: 22160541
references.citation: J Neurosci. 2011 Apr 20;31(16):6008-18
references.pmid: 21508226
references.citation: Neurosci Lett. 1987 Sep 23;80(2):158-62
references.pmid: 3317134
references.citation: J Neurosci. 2012 Oct 3;32(40):13668-78
references.pmid: 23035079
references.citation: Am J Physiol. 1971 Aug;221(2):535-43
references.pmid: 5560304
references.citation: J Neurophysiol. 2007 Dec;98(6):3121-33
references.pmid: 17913977
references.citation: Respir Physiol Neurobiol. 2013 Apr 1;186(2):214-20
references.pmid: 23454177
references.citation: Eur J Pharmacol. 1976 Oct;39(2):357-64
references.pmid: 10174
references.citation: J Comp Neurol. 1990 Dec 8;302(2):370-7
references.pmid: 2289975
references.citation: J Neurosci Methods. 1996 Apr;65(2):113-36
references.pmid: 8740589
references.citation: J Chem Neuroanat. 2009 Nov;38(3):222-30
references.pmid: 19665549
references.citation: Neuroscience. 2010 Feb 3;165(3):984-95
references.pmid: 19895871
references.citation: Br J Pharmacol. 1996 Dec;119(7):1375-84
references.pmid: 8968546
references.citation: J Appl Physiol (1985). 2001 Apr;90(4):1247-57
references.pmid: 11247921
references.citation: J Appl Physiol (1985). 2004 Dec;97(6):2303-9
references.pmid: 15322068
references.citation: J Neurophysiol. 2006 Dec;96(6):3465-73
references.pmid: 17005613
references.citation: Ann N Y Acad Sci. 2001 Jun;940:286-98
references.pmid: 11458686
references.citation: Auton Neurosci. 2006 Jun 30;126-127:106-19
references.pmid: 16580890
references.citation: J Appl Physiol (1985). 1996 Jan;80(1):108-15
references.pmid: 8847290
references.citation: Neuroscience. 1990;37(1):171-85
references.pmid: 2243591
references.citation: Respir Physiol. 1998 Jan;111(1):15-23
references.pmid: 9496468
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Jul;285(1):R110-6
references.pmid: 12609814
references.citation: J Neurophysiol. 2001 May;85(5):2224-35
references.pmid: 11353037
references.citation: J Neurophysiol. 2013 Dec;110(11):2536-44
references.pmid: 24047906
references.citation: Neuroscience. 2003;122(1):193-204
references.pmid: 14596860
references.citation: Brain Res Bull. 1992 Jan;28(1):107-13
references.pmid: 1540837
references.citation: Neuroscience. 1999 Mar;90(3):1001-11
references.pmid: 10218799
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Sep 12;364(1529):2501-16
references.pmid: 19651652
references.citation: Am J Physiol. 1999 Apr;276(4):R962-73
references.pmid: 10198373
references.citation: Neuroscience. 2014 Feb 14;259:203-13
references.pmid: 24333211
references.citation: Neuroscience. 2003;116(1):249-59
references.pmid: 12535957
references.citation: Respir Physiol. 2001 Dec;129(1-2):175-89
references.pmid: 11738653
references.citation: Brain Res. 2000 Mar 31;860(1-2):119-29
references.pmid: 10727630
references.citation: Br J Pharmacol. 2006 Dec;149(7):861-9
references.pmid: 17043669
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Aug;281(2):R528-38
references.pmid: 11448857
references.citation: J Neurosci. 2013 Feb 13;33(7):2984-93
references.pmid: 23407956
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Sep;281(3):R683-98
references.pmid: 11506981
references.citation: Respir Physiol. 1998 Feb;111(2):137-51
references.pmid: 9574866
references.citation: Neuroscience. 1996 Jul;73(2):509-18
references.pmid: 8783266
references.citation: Adv Exp Med Biol. 2008;605:338-42
references.pmid: 18085296
references.citation: Neuron. 2004 Jul 8;43(1):105-17
references.pmid: 15233921
references.citation: Synapse. 2000 Apr;36(1):21-34
references.pmid: 10700023
references.citation: Respir Physiol Neurobiol. 2014 Aug 15;200:33-9
references.pmid: 24874557
references.citation: Neurochem Res. 2000 Nov;25(11):1465-73
references.pmid: 11071365
references.citation: J Neurosci. 2013 Aug 28;33(35):13978-88, 13988a
references.pmid: 23986235
references.citation: J Neurosci. 2011 Feb 9;31(6):1981-90
references.pmid: 21307236
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1400-8
references.pmid: 19710394
references.citation: J Neurophysiol. 1995 Mar;73(3):933-44
references.pmid: 7608778
references.citation: Pflugers Arch. 2011 Sep;462(3):407-18
references.pmid: 21739157
references.citation: Brain Res. 2003 Aug 1;980(1):1-10
references.pmid: 12865154
references.citation: J Comp Neurol. 2005 Nov 28;492(4):477-94
references.pmid: 16228993
references.citation: J Comp Neurol. 1991 Nov 8;313(2):349-67
references.pmid: 1722490
references.citation: Neuroreport. 2001 Oct 29;12(15):3395-400
references.pmid: 11711893
references.citation: J Physiol. 2004 Apr 1;556(Pt 1):235-53
references.pmid: 14724193
references.citation: J Appl Physiol (1985). 2004 May;96(5):1815-24
references.pmid: 14672965
references.citation: Brain Res. 2008 May 7;1208:128-36
references.pmid: 18387596
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R411-21
references.pmid: 15031133
references.citation: Respir Physiol Neurobiol. 2010 Nov 30;174(1-2):76-88
references.pmid: 20801236
references.citation: J Physiol. 1998 Sep 1;511 ( Pt 2):433-50
references.pmid: 9706021
references.citation: Respir Physiol. 1997 Nov;110(2-3):161-76
references.pmid: 9407609
references.citation: J Comp Neurol. 1999 May 10;407(3):367-80
references.pmid: 10320217
references.citation: J Physiol. 2003 Jan 1;546(Pt 1):243-50
references.pmid: 12509492
references.citation: J Auton Nerv Syst. 1998 Aug 6;72(1):24-33
references.pmid: 9760077
references.citation: Neurosci Res. 2006 Nov;56(3):322-31
references.pmid: 16962678