title: Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats.
abstract: Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be an important determinant of phrenic LTF. Here we test the hypothesis that acute PhrX influences immediate and long-term phrenic motor responses to hypoxia. Phrenic neurograms were recorded in anesthetized, ventilated, and vagotomized adult male rats with intact phrenic nerves or bilateral PhrX. Data were obtained before (i.e., baseline), during, and after three 5-min bouts of isocapnic hypoxia. Inspiratory burst amplitude during hypoxia (%baseline) was greater in PhrX than in phrenic nerve-intact rats (P < 0.001). Similarly, burst amplitude 55 min after IH was greater in PhrX than in phrenic nerve-intact rats (175 + or - 9 vs. 126 + or - 8% baseline, P < 0.001). In separate experiments, phrenic bursting was recorded before and after PhrX in the same animal. Afferent bursting that was clearly observable in phase with lung deflation was immediately abolished by PhrX. The PhrX procedure also induced a form of facilitation as inspiratory burst amplitude was increased at 30 min post-PhrX (P = 0.01 vs. pre-PhrX). We conclude that, after PhrX, axotomy of phrenic motoneurons and, possibly, removal of phrenic afferents result in increased phrenic motoneuron excitability and enhanced LTF following IH.
authors.affiliation: Dept. of Physical Therapy, College of Public Health and Health Professions, McKnight Brain Institute, Univ. of Florida, PO Box 100154, 100 S. Newell Dr., Gainesville, FL 32610, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: K Z
authors.initials: KZ
authors.lastname: Lee
authors.forename: R F
authors.initials: RF
authors.lastname: Fregosi
authors.forename: D D
authors.initials: DD
authors.lastname: Fuller
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000503:physiopathology; D000768:Anesthesia, General; D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D001239:Inhalation; D017774:Long-Term Potentiation; D008297:Male; D009046:Motor Neurons; D010791:Phrenic Nerve / Q000503:physiopathology* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D015656:Respiratory Mechanics; D012132:Respiratory Muscles / Q000294:innervation*; D013997:Time Factors
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R1111-9
references.pmid: 16627688
references.citation: J Appl Physiol (1985). 2003 Jan;94(1):358-74
references.pmid: 12486024
references.citation: J Appl Physiol (1985). 1997 Feb;82(2):419-25
references.pmid: 9049719
references.citation: Neurosci Lett. 1991 Jan 14;122(1):117-21
references.pmid: 2057127
references.citation: Exp Neurol. 2006 Jul;200(1):74-81
references.pmid: 16647702
references.citation: J Physiol. 2004 May 15;557(Pt 1):13-8
references.pmid: 15047768
references.citation: J Neurosci. 1998 Oct 15;18(20):8436-43
references.pmid: 9763486
references.citation: J Appl Physiol (1985). 1990 Aug;69(2):640-7
references.pmid: 2228876
references.citation: Anat Rec. 1983 Feb;205(2):207-13
references.pmid: 6846871
references.citation: J Physiol. 1963 Sep;168:274-89
references.pmid: 14062677
references.citation: Am J Physiol. 1971 Aug;221(2):535-43
references.pmid: 5560304
references.citation: Respir Physiol Neurobiol. 2010 Mar 31;170(3):260-7
references.pmid: 20036763
references.citation: Respir Physiol Neurobiol. 2008 Feb 29;160(3):259-66
references.pmid: 18088567
references.citation: Brain Res. 1987 Jun 23;414(1):169-72
references.pmid: 3620920
references.citation: J Physiol. 2009 Nov 15;587(Pt 22):5469-81
references.pmid: 19805745
references.citation: Brain Res. 1996 May 6;719(1-2):239-46
references.pmid: 8782889
references.citation: J Appl Physiol (1985). 2001 Dec;91(6):2751-7
references.pmid: 11717243
references.citation: J Physiol. 2007 Dec 1;585(Pt 2):593-606
references.pmid: 17932158
references.citation: J Neurosci. 2002 Jul 15;22(14):6239-46
references.pmid: 12122082
references.citation: Anat Embryol (Berl). 1999 Dec;200(6):625-43
references.pmid: 10592066
references.citation: J Appl Physiol (1985). 2002 Jun;92(6):2565-70
references.pmid: 12015374
references.citation: J Appl Physiol (1985). 1987 Mar;62(3):941-5
references.pmid: 3571092
references.citation: J Appl Physiol (1985). 2001 Aug;91(2):709-16
references.pmid: 11457785
references.citation: J Appl Physiol (1985). 1991 Feb;70(2):491-6
references.pmid: 2022537
references.citation: J Neurosci. 1999 Feb 15;19(4):1247-56
references.pmid: 9952402
references.citation: BMC Physiol. 2005 May 06;5(1):7
references.pmid: 15877811
references.citation: J Neurobiol. 2003 Nov;57(2):204-20
references.pmid: 14556286
references.citation: J Appl Physiol (1985). 1995 Nov;79(5):1640-9
references.pmid: 8594024
references.citation: J Physiol. 2008 Apr 15;586(8):2171-81
references.pmid: 18292130
references.citation: J Appl Physiol (1985). 1986 Dec;61(6):1999-2004
references.pmid: 3027021
references.citation: J Appl Physiol (1985). 2001 May;90(5):2001-6; discussion 2000
references.pmid: 11299296
references.citation: J Neurosci. 1996 Dec 1;16(23):7469-77
references.pmid: 8922402
references.citation: J Appl Physiol (1985). 2000 May;88(5):1915-23
references.pmid: 10797157
references.citation: J Physiol. 2009 May 1;587(Pt 9):1931-42
references.pmid: 19237427
references.citation: Eur J Neurosci. 1994 Jan 1;6(1):9-17
references.pmid: 8130935
references.citation: Physiol Genomics. 2001 Jan 19;4(3):175-81
references.pmid: 11160996
references.citation: Neurosci Lett. 2008 Sep 19;442(3):213-8
references.pmid: 18652877
references.citation: Brain Res Dev Brain Res. 1990 Mar 1;52(1-2):201-9
references.pmid: 2110040
references.citation: Eur J Neurosci. 1993 Jun 1;5(6):657-68
references.pmid: 8261139
references.citation: J Appl Physiol (1985). 1987 Mar;62(3):946-51
references.pmid: 3571093
references.citation: Exp Physiol. 2007 Jan;92(1):27-37
references.pmid: 17099064
references.citation: Respir Physiol. 1998 May;112(2):123-34
references.pmid: 9716296
references.citation: Exp Neurol. 1986 Jun;92(3):624-38
references.pmid: 3709737
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4292-5
references.pmid: 15024116
references.citation: Respir Physiol. 1996 Jul;104(2-3):251-60
references.pmid: 8893371
references.citation: Nat Neurosci. 2004 Jan;7(1):48-55
references.pmid: 14699417
references.citation: Prog Neurobiol. 1990;35(1):1-51
references.pmid: 2217820
references.citation: J Neurophysiol. 1998 Mar;79(3):1371-83
references.pmid: 9497418
references.citation: J Appl Physiol (1985). 1986 Mar;60(3):854-60
references.pmid: 3957836
references.citation: J Appl Physiol (1985). 2005 May;98(5):1761-7
references.pmid: 15640385
references.citation: J Appl Physiol (1985). 2001 Jun;90(6):2466-75
references.pmid: 11356815
references.citation: J Physiol. 2009 Nov 15;587(Pt 22):5451-67
references.pmid: 19805747
references.citation: J Neurophysiol. 2009 Oct;102(4):2184-93
references.pmid: 19657076
references.citation: Respir Physiol. 2000 Jul;121(2-3):135-46
references.pmid: 10963770
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1979 Jun;46(6):1096-1102
references.pmid: 468630
references.citation: Neurosci Lett. 2005 Jun 3;380(3):330-4
references.pmid: 15862912
references.citation: J Neurosci. 1990 Nov;10(11):3564-75
references.pmid: 2230946
references.citation: J Neurosci. 2003 May 1;23(9):3715-25
references.pmid: 12736342
references.citation: Neuroscience. 2008 Mar 3;152(1):189-97
references.pmid: 18207649
references.citation: Respir Physiol Neurobiol. 2008 Jun 30;162(1):8-17
references.pmid: 18450525
references.citation: Lung. 1990;168(3):137-49
references.pmid: 2114507
references.citation: J Appl Physiol (1985). 2003 Jan;94(1):399-409
references.pmid: 12391138
references.citation: FASEB J. 2004 Dec;18(15):1934-6
references.pmid: 15451889