title: Defining the neurocircuitry of exercise hyperpnoea.
abstract: One hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid-brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for 'central command'. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Sherrington Building, Parks Road, Oxford OX1 3PT, UK. david.paterson@dpag.ox.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
mesh_terms: D001921:Brain / Q000502:physiology*; D058256:Brain Waves; D015444:Exercise; D006801:Humans; D008168:Lung / Q000294:innervation / Q000502:physiology*; D012123:Pulmonary Ventilation
references.citation: Respir Physiol. 1989 Dec;78(3):323-30
references.pmid: 2616927
references.citation: Neuroreport. 2005 Nov 7;16(16):1741-5
references.pmid: 16237319
references.citation: J Physiol. 1988 May;399:437-49
references.pmid: 3136247
references.citation: J Physiol. 2001 Jun 15;533(Pt 3):823-36
references.pmid: 11410638
references.citation: Auton Neurosci. 2013 Apr;175(1-2):17-25
references.pmid: 23336968
references.citation: J Physiol. 2002 Mar 1;539(Pt 2):615-21
references.pmid: 11882692
references.citation: J Physiol. 1990 Oct;429:339-48
references.pmid: 2277352
references.citation: J Neurophysiol. 1983 Mar;49(3):582-94
references.pmid: 6300351
references.citation: J Physiol. 1987 Mar;384:109-18
references.pmid: 3656144
references.citation: Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H137-44
references.pmid: 12649075
references.citation: J Physiol. 1971 Jul;215(3):789-804
references.pmid: 5090995
references.citation: J Physiol. 1913 Oct 17;47(1-2):112-36
references.pmid: 16993229
references.citation: Brain Res. 1988 Sep 20;460(2):339-45
references.pmid: 2465061
references.citation: Respir Physiol. 1988 Nov;74(2):229-37
references.pmid: 3227179
references.citation: Physiol Rev. 1982 Jan;62(1):262-346
references.pmid: 6798585
references.citation: Respir Physiol. 1993 Aug;93(2):203-19
references.pmid: 8210759
references.citation: J Physiol. 1995 Dec 15;489 ( Pt 3):663-75
references.pmid: 8788932
references.citation: J Physiol. 1984 Oct;355:85-97
references.pmid: 6436482
references.citation: Respir Physiol. 1998 Nov;114(2):109-17
references.pmid: 9865585
references.citation: Eur J Appl Physiol Occup Physiol. 1986;55(5):530-7
references.pmid: 3769910
references.citation: J Physiol. 1988 Jul;401:519-31
references.pmid: 3139872
references.citation: J Physiol. 2013 Jan 1;591(1):109-22
references.pmid: 23129795
references.citation: Brain Res. 1988 Jan 26;439(1-2):95-106
references.pmid: 3359200
references.citation: Sports Med. 2013 Apr;43(4):227-41
references.pmid: 23456492
references.citation: J Appl Physiol (1985). 1987 May;62(5):1767-71
references.pmid: 3597249
references.citation: J Physiol. 1972 Jul;224(1):173-86
references.pmid: 5039977
references.citation: J Physiol. 2007 Jan 15;578(Pt 2):605-12
references.pmid: 17082229
references.citation: AJNR Am J Neuroradiol. 2000 Sep;21(8):1502-9
references.pmid: 11003287
references.citation: J Physiol. 1928 Dec 20;66(4):323-45
references.pmid: 16993996
references.citation: Physiol Rev. 1950 Apr;30(2):220-39
references.pmid: 15424035
references.citation: J Physiol. 1990 Jan;420:281-93
references.pmid: 2324985
references.citation: J Appl Physiol. 1973 Aug;35(2):236-43
references.pmid: 4723033
references.citation: J Appl Physiol (1985). 2011 Apr;110(4):881-91
references.pmid: 21164158
references.citation: Respir Physiol. 1985 Jan;59(1):65-70
references.pmid: 3975503
references.citation: Exp Physiol. 2012 Jan;97(1):29-38
references.pmid: 21984730
references.citation: J Appl Physiol (1985). 2004 Jan;96(1):301-7
references.pmid: 12972440
references.citation: Am Rev Respir Dis. 1975 Aug;112(2):219-49
references.pmid: 239617
references.citation: Brain Res. 1996 Jul 8;726(1-2):109-22
references.pmid: 8836551
references.citation: Am J Physiol. 1960 Jun;198:1139-42
references.pmid: 13832112
references.citation: Pain. 1985 Mar;21(3):241-252
references.pmid: 3991230
references.citation: J Physiol. 1905 May 9;32(3-4):225-66
references.pmid: 16992774
references.citation: Eur J Appl Physiol Occup Physiol. 1995;71(1):1-27
references.pmid: 7556128
references.citation: Compr Physiol. 2012 Jan;2(1):743-77
references.pmid: 23728984
references.citation: Trends Neurosci. 1994 Sep;17(9):379-89
references.pmid: 7817403
references.citation: J Lab Clin Med. 1966 Aug;68(2):279-85
references.pmid: 5912602
references.citation: Am J Physiol. 1989 Feb;256(2 Pt 2):R348-56
references.pmid: 2644848
references.citation: Exp Neurol. 2013 Jan;239:248-55
references.pmid: 23127542
references.citation: J Comp Neurol. 1998 Nov 30;401(4):455-79
references.pmid: 9826273
references.citation: Science. 1981 Feb 20;211(4484):844-6
references.pmid: 7466362
references.citation: Cardiovasc Res. 1990 Oct;24(10):821-33
references.pmid: 2085837
references.citation: Proc Biol Sci. 1991 Jun 22;244(1311):241-6
references.pmid: 1679944
references.citation: Neuroreport. 1999 Mar 17;10(4):681-5
references.pmid: 10208530
references.citation: J Neurosci. 2008 Nov 19;28(47):12274-83
references.pmid: 19020021
references.citation: Brain Res Bull. 1990 Mar;24(3):437-55
references.pmid: 1970946
references.citation: Respir Physiol. 1998 Dec;114(3):201-11
references.pmid: 9926985
references.citation: Exp Physiol. 2010 Nov;95(11):1043-8
references.pmid: 20696787
references.citation: J Physiol. 1987 Mar;384:1-26
references.pmid: 3116208
references.citation: J Physiol. 1909 Jun 15;38(5):420-40
references.pmid: 16992963
references.citation: J Physiol (Paris). 1959 Mar-Apr;51(2):163-261
references.pmid: 13655208
references.citation: J Physiol. 1954 Jul 28;125(1):118-37
references.pmid: 13192760
references.citation: J Physiol. 2009 Nov 1;587(Pt 21):5149-62
references.pmid: 19752114
references.citation: J Physiol. 1977 Nov;272(3):553-61
references.pmid: 592202
references.citation: Neurology. 2012 Jan 17;78(3):210-7
references.pmid: 22249496
references.citation: J Appl Physiol. 1975 Sep;39(3):354-8
references.pmid: 240799
references.citation: Pflugers Arch. 2012 Aug;464(2):155-66
references.pmid: 22665049
references.citation: J Appl Physiol (1985). 2010 Oct;109(4):966-76
references.pmid: 20634355
references.citation: J Appl Physiol (1985). 1992 Mar;72(3):811-20
references.pmid: 1314799
references.citation: J Appl Physiol (1985). 2001 Apr;90(4):1392-9
references.pmid: 11247939
references.citation: J Physiol. 1972 Oct;226(1):173-90
references.pmid: 4263680