Learning to breathe: control of the inspiratory-expiratory phase transition shifts from sensory- to central-dominated during postnatal development in rats.
The hallmark of the dynamic regulation of the transitions between inspiration and expiration is the timing of the inspiratory off-switch (IOS) mechanisms. IOS is mediated by pulmonary vagal afferent feedback (Breuer-Hering reflex) and by central interactions involving the Kölliker-Fuse nuclei (KFn). We hypothesized that the balance between these two mechanisms controlling IOS may change during postnatal development. We tested this hypothesis by comparing neural responses to repetitive rhythmic vagal stimulation, at a stimulation frequency that paces baseline breathing, using in situ perfused brainstem preparations of rats at different postnatal ages. At ages < P15 (P, postnatal days), phrenic nerve activity (PNA) was immediately paced and entrained to the afferent input and this pattern remained unchanged by repetitive stimulations, indicating that vagal input stereotypically dominated the control of IOS. In contrast, PNA entrainment at > P15 was initially insignificant, but increased after repetitive vagal stimulation or lung inflation. This progressive adaption of PNA to the pattern of the sensory input was accompanied by the emergence of anticipatory centrally mediated IOS preceding the stimulus trains. The anticipatory IOS was blocked by bilateral microinjections of NMDA receptor antagonists into the KFn and PNA was immediately paced and entrained, as it was seen at ages < P15. We conclude that as postnatal maturation advances, synaptic mechanisms involving NMDA receptors in the KFn can override the vagally evoked IOS after 'training' using repetitive stimulation trials. The anticipatory IOS may imply a hitherto undescribed form of pattern learning and recall in convergent sensory and central synaptic pathways that mediate IOS.
Dutschmann
Mathias
M
Institute for Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK. m.dutschmann@leeds.ac.uk
Mörschel
Michael
M
Rybak
Ilya A
IA
Dick
Thomas E
TE
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D045853:Exhalation / Q000187:drug effects / Q000502:physiology*; D001239:Inhalation / Q000187:drug effects / Q000502:physiology*; D007858:Learning; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development*; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate
J Appl Physiol (1985). 2006 Aug;101(2):618-27
16645192
Acta Neurobiol Exp (Wars). 1980;40(3):543-62
7435267
J Neurophysiol. 1987 Dec;58(6):1259-74
3437333
J Physiol. 2007 Mar 15;579(Pt 3):863-76
17204503
Respir Physiol. 1995 Sep;101(3):219-30
8606995
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):281-92
15519561
J Appl Physiol (1985). 2006 Aug;101(2):628-34
16601307
J Neurosci. 1994 Nov;14(11 Pt 1):6500-10
7965054
J Appl Physiol (1985). 1998 Dec;85(6):2033-9
9843523
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):307-19
15519563
J Physiol. 2008 May 1;586(9):2331-43
18339694
Biol Neonate. 1994;65(3-4):205-10
8038284
Acta Neurobiol Exp (Wars). 1981;41(1):87-94
7270255
Pflugers Arch. 1984 Jul;401(3):281-6
6473081
Exp Brain Res. 1999 Nov;129(2):191-200
10591893
Behav Brain Funct. 2006 Aug 08;2:29
16893471
Auton Neurosci. 2000 Oct 30;84(1-2):19-29
11109986
Respir Physiol. 2001;124(1):51-64
11084203
J Neurophysiol. 2002 Feb;87(2):1057-67
11826069
J Neurophysiol. 2007 Dec;98(6):3370-87
17913982
J Comp Neurol. 1990 Mar 22;293(4):540-80
1691748
Neuroscience. 2006 Aug 25;141(2):1011-1023
16725272
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):155-65
15519552
Respir Physiol. 1975 Jan;23(1):71-85
1129551
Neuroreport. 1996 May 31;7(8):1432-6
8856692
J Appl Physiol (1985). 1994 Mar;76(3):1138-43
8005856
J Neurophysiol. 2005 May;93(5):2674-87
15601729
Brain Res. 2000 Oct 13;880(1-2):118-30
11032996
J Neurosci. 1996 Oct 15;16(20):6526-36
8815930
J Neurosci. 2006 May 24;26(21):5825-34
16723541
Curr Opin Neurobiol. 2001 Jun;11(3):327-35
11399431
Prog Brain Res. 2007;165:201-20
17925248
Brain Res. 1994 Jul 25;652(1):83-6
7953724
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):127-40
15519550
J Physiol. 2000 Jun 1;525 Pt 2:283
10835032
J Comp Neurol. 1989 Mar 1;281(1):69-96
2466879
Neurosci Res. 2002 Sep;44(1):101-10
12204298
J Neurosci. 1985 Nov;5(11):2909-19
2865341
Exp Brain Res. 1992;89(3):623-39
1386575
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):167-75
15519553
Brain Res Bull. 1997;42(4):323-34
9043719
J Physiol. 2000 Mar 1;523 Pt 2:479-91
10699090
Nat Rev Neurosci. 2005 Jun;6(6):477-83
15928717
J Neurosci. 2000 May 1;20(9):RC73
10777815
Eur J Neurosci. 2007 Dec;26(12):3449-57
18052976
Eur J Neurosci. 2006 Aug;24(4):1071-84
16930433
Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):72-9
18620081
J Neurophysiol. 2008 Oct;100(4):1770-99
18650310
Physiol Rev. 1995 Jan;75(1):1-45
7831394
J Appl Physiol (1985). 1992 Feb;72(2):721-30
1559953
J Comp Neurol. 1994 Sep 1;347(1):64-86
7798382
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):105-14
15519548
J Auton Nerv Syst. 1993 Feb;42(2):99-118
8383713
J Appl Physiol (1985). 1988 Sep;65(3):1033-9
3182471
J Neurophysiol. 2008 Oct;100(4):1749-69
18632881
Respir Physiol. 1994 May;96(2-3):177-88
7914709
Annu Rev Psychol. 1972;23:73-104
4335280
J Physiol. 2007 Aug 15;583(Pt 1):315-27
17569735
J Neurosci Methods. 1996 Mar;65(1):63-8
8815310
Respir Physiol Neurobiol. 2004 Nov 15;143(2-3):321-32
15519564
J Physiol. 1993 May;464:725-45
8229827
J Neurophysiol. 2004 Oct;92(4):2394-404
15152019
J Comp Neurol. 1999 Dec 27;415(4):501-17
10570458
J Physiol. 2008 Sep 1;586(17):4265-82
18599543
Brain Res. 1990 Apr 9;513(1):35-42
2350683
J Comp Neurol. 2002 Apr 22;446(1):81-94
11920722
Prog Neurobiol. 1998 Oct;56(1):97-117
9723132