The neuronal mechanisms of respiratory rhythm generation

Current Opinion in Neurobiology

Volumn 6, Issue 6, 1996, Pages 817-825

  Ramirez, Jan Marino ^a   Richter, Diethelm W ^b  

^a UNIVERSITY OF CHICAGO   (United States)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN STEM; BREATHING RATE; MEDULLA OBLONGATA; NONHUMAN; PRIORITY JOURNAL; RESPIRATION CONTROL; RESPIRATORY NERVE CELL; REVIEW;

EID: 0030467938     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(96)80033-X     Document Type: Article

References (85)

1. Funk GD, Feldman JL: Generation of respiratory rhythm and pattern in mammals: insights from developmental studies. Curr Opin Neurobiol 1995, 5:778-785. A recent review that summarizes our current views of respiratory rhythm generation, particularly emphasizing the postnatal changes occurring within the respiratory network.
2. Smith JC, Funk GD, Johnson SM, Feldman JL: Cellular and synaptic mechanisms generating respiratory rhythm: insights from in vitro and computational studies. In Ventral Brainstem Mechanisms and Control of Respiration and Blood Pressure. Edited by Trouth CO, Willis R, Kiwull-Schone H, Schlaefke M. New York: Marcel Dekker; 1995:463-496. A detailed description of the hybrid pacemaker network model. A particularly important role in rhythm generation is attributed to pacemaker neurons, which together with synaptic inputs ('hybrid network') lead to the generation of the respiratory rhythm.
3. Duffin J, Ezure K, Lipski J: Breathing rhythm generation: focus on the rostral ventrolateral medulla. News Physio! Sei 1995, 10:133-140. Reviews the mechanisms of respiratory rhythm generation, with an emphasis on the role of synaptic inhibition in the cat in vivo.
4. Bonham AC: Neurotransmitters in the CMS control of breathing. Respir Physiol 1996, 101:219-230. Gives an overview of the known neurotransmitters and modulators that are involved in generating the respiratory rhythm.
5. Bianchi AL, Denavit-Saubie M, Champagnat J: Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters. Physiol Rev 1995, 75:1-45. A very detailed description of the known synaptic and intrinsic membrane properties that lead to the generation of the respiratory rhythm. Particular emphasis is given to the modulation of the respiratory rhythm.
6. Richter DW: Neural regulation of respiration: rhythmogenesis and afferent control. In Comprehensive Human Physiology, vol 2. Edited by Greger R, Windhorst U. Berlin: Springer Verlag; 1996:2079-2095. This book chapter reviews in great detail the central mechanisms of respiratory rhythm generation, and it also describes the modulation of the respiratory network by afferent input.
7. Richter DW, Ballanyi K, Ramirez JM: Respiratory rhythm generation. In Neural Control of the Respiratory Muscles. Edited by Miller AD, Bianchi AL, Bishop BP. Boca Raton: CRC Press; 1996:119-131. This review focusses on the central mechanisms of respiratory rhythm generation. Special reference is given to the complex interaction between synaptic and intrinsic membrane properties.
8. Ommaru H: Studies of the respiratory center using isolated brainstem-spinal cord preparations. Neurose/ Res 1995, 21:183-190. A review focussing on respiratory rhythm generation, with a particular emphasis on the role of pre-inspiratory neurons.
9. Richter DW, Ballantyne D, Remmers JE: Respiratory rhythm generation: a model. News Physiol Sei 1986, 1:109-111.
10. Innés JA, Morrell MJ, Kobayashi I, Hamilton RD, Guz A: Central and reflex neural control of genioglossus in subjects who underwent laryngectomy. J Appl Physiol 1995, 78:2180-2186.
11. Simon PM, Leevers AM, Murty JL, Skatrud JB, Dempsey JA: Neuromechanical regulation of respiratory motor output in ventilator-dependent C1-C3 quadriplegics. J Appl Physiol 1995, 79:312-322. Demonstrates that in humans, afferent feedback from the chest wall is involved in a volume- and frequency-dependent modulation of inspiratory muscle activity.
12. Miller AD, Yamaguchi I, Siniaia MS, Yates BJ: Ventral respiratory group bulbospinal inspiratory neurons participate in vestibularrespiratory reflexes. J Neurophysiol 1995, 73:1303-1307.
13. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL: Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 1991, 254:726-729.
14. Fung M-L, Wang W, St John WM: Medullary loci critical for expression of gasping in adult rats. J Physio/ (Land) 1994, 480:597-611.
15. Ramirez JM, Pierrefiche O, Schwarzacher SW, Filloux F, Mclntosh JM, Olivera BM, Richter DW: The influence of N-type calcium channel blockers on the respiratory network of adult cats. Soc Neurosci Abstr 1994, 20:1755.
16. Koshiya N, Guyenet PG: Tonic sympathetic chemoreflex after blockade of respiratory rhythmogenesis in the rat J Physiol (Land) 1996, 491:859-869. Injection of muscimol into the pre-Bötzinger complex of rats in vivo eliminates respiratory activity. Using this approach, the authors suggest that the sympathetic response to chemoreceptor stimulation is attributable to two inputs converging in the rostral ventrolateral medulla: a respiration-independent excitatory input and a respiratory rhythmic input originating from the pre-Bötzinger complex.
17. 7. Funk GD, Smith JC, Feldman JL: Development of thyrotropinreleasing hormone and norepinephrine potentiation of inspiratory related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro. J Neurophysiol 1994, 72:2538-2541.
18. Ramirez JM, Quellmalz UJA. Richter DW: Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice. J Physiol (Land) 1996, 491:799-812. Demonstrates that respiratory rhythmic activity can be maintained in a transverse brainstem slice preparation from mice up to the age of 22 postnatal days. Even at more mature stages, respiratory rhythmic activity persists after blockade of glycinergic receptors with strychnine.
19. Greer JJ, Carter JE, Allan DW: Respiratory rhythm generation in a precocial rodent in vitro preparation. Respir Physiol 1996, 103:105-112. In a mouse species that is born at a relatively mature state, respiratory rhythmic activity persists in the presence of strychnine. This indicates that in the in vitro animal preparation, synaptic inhibition is not essential for the generation of the respiratory rhythm, irrespective of age.
20. Schwarzacher SW, Smith JC, Richter DW: Pre-Bötzinger complex in the cat J Neurophysiol 1995, 73:1452-1461. In vivo intracellular recordings demonstrate that all known types of respiratory neurons are present in the pre-Bötzinger complex of adult cats.
21. Connelly CA, Dobbins EG, Feldman JL: Pre-Bötzinger complex in cats: respiratory neuronal discharge patterns. Brain Res 1992, 390:337-340.
22. Gozal D, Omidvar O, Kirlew KAT, Hathout GM, Hamilton R, Lufkin RB, Harper RM: Identification of human brain regions underlying responses to resistive inspiratory loading with functional magnetic resonance imaging. Proc Natl Acad Sei USA 1995, 92:6607-6611.
23. Dick TE, Bellingham MC, Richter DW: Pontine respiratory neurons in anaesthetized cats. Brain Res 1995, 636:259-269. Respiratory neurons located within the pons are characterized by intracellular recordings in the adult cat.
24. Katz DM: Transmitter plasticity in developing chemoafferent neurons. Physiologist 1996, 39:194.
25. Fortin G, Kato F, Lumsden A, Champagnat J: Rhythm generation in the segmented hindbrain of chick embryos. J Physiol (Land) 1995,486:735-744. The existence of a segmented rhythm-generating network is demonstrated within the hindbrain of chick embryos. This embryonic network determines the anatomical and physiological fate of neurons in this region. The rhythmgenerating networks of different segments have different rhythmgenic properties. It is hypothesized that these networks reflect an early state of the neuronal network generating respiratory-related activities.
26. Champagnat J: Early ontogeny of rhythm generation and control of breathing. Physiologist 1996, 39:193.
27. Morrison S: Respiratory modulation of sympathetic nerve activity: effect of MK-801. Am J Physiol 1996, 270:R645-R651. In decerebrate, unanesthetized, vagotomized and artificially ventilated rats, blockade of NMDA channels with MK-801 leads to an increase in the duration of inspiration and a reduction in phrenic nerve amplitude.
28. Kanjhan R, Lipski J, Kruszewska B, Rong W: A comparative study of presynaptic and Bötzinger neurons in the rostral ventrolateral medulla (RVLM) of the rat Brain Res 1995, 699:19-32. Anatomically adjacent pre-sympathetic and Bötzinger expiratory neurons form two functionally distinct neuronal subpopulations.
29. Lipski J, Kanjhan R, Kruszewska B, Rong WF, Smith M: Pre sympathetic neurones in the rostral ventrolateral medulla of the rat: electrophysiology, morphology and relationship to adjacent neuronal groups. Acta Neurobiol Exp 1996, 56:373-384. The activity of pre-sympathetic neurons in the rostral ventrolateral medulla depends largely on synaptic excitation from antecedent reticulospinal neurons. This study emphasizes that network properties are critical for the generation of the sympathetic vasomotor tone.
30. Ramirez JM, Teigkamp P, Eisen FP, Richter DW: Gasp-like activity in the transverse rhythmic slice preparation of mice. Soc Neurosd Abstr 1996, 22:543.12.
31. Nakamura Y, Katakura N: Generation of masticatory rhythm in the brainstem. Neurosci Res 1995, 23:1 -9. This review summarizes our current knowledge of mastication.
32. Katakura N, Jia L, Nakamura Y: NMDA-induced rhythmical activity in XII nerve of isolated CMS from newborn rats. Neuroreport 1995, 6:601-604.
33. McFarland DH, Lund JP: Modification and respiration during swallowing in the adult human. J Neurophysiol 1995, 74:1509-1517. The muscles of the jaws are activated by various behaviours, such as mastication, respiration, vocalization, deglutition or swallowing. The underlying neural networks localized within the brainstem require a complex coordination. This study deals with the coordination between mastication and respiration, rhythmic activities that have to be interrupted during swallowing
34. Dobbins EG, Feldman JL: Differential innervation of protruder and retractor muscles of the tongue in rat J Comp Neurol 1995, 357:376-394. Tongue movements are activated during mastication, respiration, swallowing and vocalization. This study uses the transsynaptic transport capabilities of pseudorabies virus to determine specific circuits that innervate protruder and retractor muscles of the rat tongue. The two muscles exhibit defined functional differences. The protruder muscle maintains airway patency and is phasically activated during inspiration. Retractor muscles are inactive during respiration but are crucial for the initiation of swallowing. The data suggest an anatomical segregation of functional networks that control hypoglossal motoneurons.
35. Tomori Z, Fung M-L, Donic V, Donicova V, St John WM: Power spectral analysis of respiratory responses to pharyngeal stimulation in cats: comparisons with eupnoea and gasping. J Physiol (Lond) 1996, 485:551-559. Mechanical stimulation of the pharynx suppresses respiration and activates gasping. Both activities are characterized by significantly different power and coherence spectra, supporting the concept that separate brainstem mechanisms generate normal respiration and gasping.
36. Fung M-L, Tomori Z, St John WM: Medullary neuronal activities in gasping induced by pharyngeal stimulation and hypoxia. Respir Physiol 1995, 100:195-202. Provides further evidence that different brainstem mechanisms are responsible for generating normal respiration and gasping.
37. Richter DW: Generation and maintenance of the respiratory rhythm. J Exp S/o/1983, 100:93-107.
38. Schmid K, Foutz AS, Denavit-Saubie M: Inhibition mediated by glycine and GABAA receptors shape the discharge pattern of bulbar respiratory neurons. Brain Res 1996, 710:150-160. Demonstrates under in vivo conditions that synaptic inhibition is critical for the inspiratory off-switch and for shaping inspiratory activity. The differential role of GABAergic and glycinergic inhibition is characterized in detail by ionotophoretic application of agonists and antagonists.
39. Duff i n J, Van Alphen J: Cross-correlation of augmenting expiratory neurons of the Bötzinger complex in the cat Exp Brain Res 1995, 103:251-255. The existence of reciprocal inhibition is demonstrated between augmenting expiratory neurons of the ipsi- and contralateral Bötzinger complex. The authors discuss the possibility that these connections synchronize expiratory bursts of activity within this synergistic neuronal population.
40. Reckling JC, Champagnat J, Denavit-Saubie M: Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro. J Neurophysiol 1996, 75:795-810. The authors characterize three types of inspiratory neurons that have distinct electrophysiological properties, as well as very characteristic discharge patterns in the respiratory cycle.
41. Onimaru H, Arata A, Homma I: Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats. Exp Brain Res 1995, 106:57-68. Bursting properties are characterized for one specific type of inspiratory neuron: the pre-inspiratory neuron. In the brainstem/spinal-cord preparation, these neurons possess intrinsic bursting properties that are not attributable to phasic synaptic inputs. The role of these bursting properties in the generation of the overall respiratory rhythm is discussed.
42. Johnson SM, Smith JC, Funk GD, Feldman JL: Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat J Neurophysiol 1994, 72:2598-2608.
43. Smith JC, Gréer JJ, Liu G, Feldman JL: Neural mechanisms generating respiratory pattern in mammalian brainstem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity. J Neurophysiol 1990, 64:1149-1167.
44. Onimaru H, Ballanyi K, Richter DW: Calcium-dependent responses in neurons of the isolated respiratory network of newborn rats. J Physio/ (Lond) 1996, 491:677-695. Different types of calcium currents are characterized in respiratory neurons of neonatal rats under current clamp conditions using the brainstem/spinal-cord preparation.
45. Eisen FP, Teigkamp P, Ramirez JM, Richter DW: Calcium currents in neurons of the isolated respiratory system of mice. Soc Neurosci Abstr 1996, 22:627.4.
46. Richter DW, Champagnat J, Jaquin T, Benacka R: Calcium currents and calcium-dependent potassium currents in mammalian medullary respiratory neurones. J Physio/ (Lond) 1993, 470:23-33.
47. Mifflin SW, Richter DW: Effects of OX-314 on medullary respiratory neurons. Brain Res 1987, 420:22-31.
48. Greer JJ, Smith JC, Feldman JL: Role of excitatory amino acids in the generation and transmission of respiratory drive in neonatal rat brainstem-spinal cord in vitro. J Physio/ (Lond) 1991,437:727-749.
49. Funk GD, Smith JC, Feldman JL: Modulation of neural network activity in vitro by cyclothiazide, a drug that blocks desensitization of AMPA receptors. J Neurosci 1995, 15:4046-4056. The authors demonstrate that AMPA receptors play a role in the generation of respiratory activity. Blockade of AMPA receptor desensitization with cyclothiazide increases significantly the frequency and amplitude of respiratory rhythmic activity.
50. Foutz AS, Pierrefiche O, Denavit-Saubie M: Combined blockade of NMDA and non-NMDA receptors produces respiratory arrest in the adult cat Neuroreport 1994, 5:481-484.
51. Feldman JL, Windhorst U, Anders K, Richter DW: Synaptic interaction between medullary respiratory neurones during apneusis induced by NMDA-receptor blockade in cat J Physio/ (Lond) 1992, 450:303-323.
52. Ramirez JM: The role of bursting properties in neuronal circuits involved in the generation of rhythmic motor pattern in invertebrates and vertebrates. In Nervous Systems and Behaviour. Proceedings of the 4th International Congress on Neuroethology. Edited by Burrows M, Matheson T, Newland PL, Schuppe H. New York: Thieme Verlag; 1995:96. The state-dependent role of bursting properties in amplifying synaptic input is described for different motor systems, including the mammalian respiratory system.
53. Champagnat J, Richter DW: The roles of K+ conductance in expiratory pattern generation in anaesthetized cats. J Physiol (Lond) 1994, 479:127-138.
54. Bayliss DA, Viana F, Bellingham MC, Berger AJ: Characteristics and postnatal development of a hyperpolarisation-activated inward current in rat hypoglossal motoneurons in vitro. J Neurophysiol 1994, 71:119-128.
55. Dong X-W, Feldman JL: Modulation of inspiratory drive to phrenic motoneurons by presynaptic adenosine A1 receptors. J Neurosci 1996, 15:3458-3467. Using patch-clamp recordings from phrenic motoneurons in the in vitro brainstem/spinal-cord preparation of neonatal rats, the authors demonstrate that adenosine enhances presynaptically the inspiratory drive to phrenic motoneurons.
56. Greer JJ, Carter JE, Al-Zubaidy Z: Opioid depression of respiration in neonatal rats. J Physiol (Lond) 1995, 485:845-855. Using different in vitro and in vivo approaches, the authors demonstrate that the opioid-induced suppression of the frequency of respiratory activity in neonatal rats is attributable to the activation of mu-opioid receptors that are localized within the pre-Bötzinger complex. Delta-opioid activation develops later, in the second postnatal week.
57. Kawai A, Okada Y, Mueckenhoff K, Scheid P: Theophylline and hypoxic ventilatory response in the rat isolated brainstem-spinal cord. Respir Physiol 1995, 100:25-32. In the isolated brainstem/spinal-cord, the authors demonstrate that theophylline attenuates hypoxia-induced respiratory depression at a concentration that is known to block adenosine receptors. A similar effect was observed in the presence of the specific adenosine antagonist SPT (8-p-sulfophenyltheophylline).
58. Burton MD, Nouri M, Kazemi H: Acetylcholine and central respiratory control: perturbations of acetylcholine synthesis in the isolated brainstem of the neonatal rat Brain Res 1995, 670:39-47.
59. Ide T, Shirahata M, Chou C-L, Fitzgerald RS: Effects of a continuous infusion of dopamine on the ventilatory and carotid body responses to hypoxia in cats. Clin Exp Pharmacol Physiol 1995,22:658-664.
60. Barraco RA, Clough-Helfman C, Goodwin BP, Anderson GF: Evidence for presynaptic adenosine A2a receptors associated with norepinephrine release and their desensitization in the rat nucleus tractus solitarius. J Neurochem 1995, 65:1604-1611.
61. McCrimmon DR, Dekin MS, Mitchell GS: Glutamate, GABA and serotonin in ventilatory control. In Lung Biology in Health and Disease Regulation of Breathing: Central Nervous Control, vol 79. Edited by Dempsey JA, Pack AI. New York: Marcel-Dekker; 1995:151-218. This very detailed review describes the role of the neuromodulator serotonin in several forms of modulation and plasticity. Although the discussion focusses largely on central brainstem/spinal cord mechanisms, emphasis is given on the impact of neuromodulation in the intact, behaving animal.
62. Kinney H, Panigraphy A, Rava LA, White WF: Three-dimensional distribution of [SHlquinuclidnyl benzilate binding to muscarinic cholinergic receptors in the developing human brainstem. J Comp Neurol 1995, 362:350-367. Shows that cholinergic receptors are differentially distributed within the human brainstem. In general, binding levels decrease during the last half of gestation, and the relative distribution at birth is similar to that in adults.
63. Fodor M, Gallatz K, Palkovits M: Calcitonin gene-related peptide innervation of A2-catecholamine cells in the nucleus of the solitary tract of the rat Brain Res 1995, 690:141 -144.
64. Mallios VJ. Lydie R, Baghoyan HA: Muscarinic receptor subtypes are differentially distributed across brainstem respiratory nuclei. Am J Physiol 1995, 268:L941 -L949. Using in vitro receptor autoradiography, the authors demonstrate that M1, M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes are differentially distributed in cat brainstem regions that are known to regulate breathing. The greatest amount was found in the lateral NTS, and fewer mAChRs were localized in nuclei of the ventral respiratory group (nucleus ambiguus, retrofacial nucleus) and ventral medulla (retrotrapezoid nucleus and ventrolateral medulla).
65. Zee N, Filiano JJ, Panigrahy A, White WF, Kinney HC: Developmental changes in [SHllysergic acid diethylamide (E3H1LSD) binding to serotonin receptors in the human brainstem. J Neuropathol Exp Neurol 1996, 55:114-126. The highest levels of LSD binding occurred prenatally throughout the brainstem, and a marked decline occurred between the mid-gestation and infancy in various brainstem regions that are involved in the control of breathing. The data are consistent with a trophic role of serotonin in the immature human brainstem. At all ages, the highest binding was observed in the rostral raphe nucleus, which is known to play a role in serotonergic modulation of vegetative functions controlled by the brainstem.
66. Zhang C, Moss IR: Age-related mu, delta, kappa-opioid ligands in respiratory-related brain regions of piglets: effect of prenatal cocaine. Dev Brain Res 1995, 87:188-193. Opioid content is higher in respiratory-related brain regions of young than older piglets. Increased content was observed after cocaine exposure in both age groups, but more in the young animals. This finding suggests that high opioid content may contribute to the relatively higher respiratory suppression in early life, such as apnea or periodic breathing. It may also contribute to the exaggerated respiratory dysrhythmia observed in neonates pre-exposed to cocaine.
67. + channels are functional in expiratory neurones of normoxic cats. J Physiol (Land) 1996, 494:399-409. ATP-dependent potassium channels are involved in modulating respiratory discharge of expiratory neurons, even under normoxic conditions, as shown in the adult cat.
68. Lalley PM, Bischoff AM, Richter DW: Serotonin 1A-receptor activation suppresses respiratory apneusis in the cat Neurosci Lett 1994, 172:59-62.
69. Haji A, Pierrefiche O, Lalley PM, Richter DW: Protein kinase C pathways modulate respiratory pattern generation in the cat J Physiol (Land) 1996, 494:297-306. The protein kinase C pathways are endogenously active in respiratory neurons that modulate their activity by downregulating persistent potassium currents, upregulating excitatory postsynaptic currents (EPSCsj and chloridemediated inhibitory postsynaptic currents (IPSCs).
70. Wilken B, Lalley P, Bischoff AM, Christen HJ, Behnke J, Hanefeld F, Richter DW: Treatment of apneustic respiratory disturbance with a serotonin receptor agonist J Pediatr 1996, in press. An agonist for 5-HT] A receptors (buspirone) can convert prolonged inspiratory activity (apneusis) to normal respiratory activity. In this study, the authors demonstrate that this modulatory effect is of direct clinical relevance, as it can be used to treat successfully severe apneusis.
71. Reckling JC, Champagnat J, Denavit-Saubie M: Thyrotropin releasing hormone (TRH) depolarizes a subset of inspiratory neurons in the newborn mouse brainstem in vitro. J Neurophysiol 1996, 75:811 -818. Thyrotropin-releasing hormone (TRH) increases the frequency of the respiratory rhythm in newborn mice. It depolarizes a subset of inspiratory neurons postsynaptically, without changing their input resistance. This depolarizing effect of TRH may be responsible for the overall respiratory effect.
72. Greer JJ, Al-Zubaidy Z, Carter JE: Thyrotropin-releasing hormone (TRH) stimulates perinatal rat respiration in vitro. Am J Physiol 1996, in press. The authors demonstrate in different in vitro preparations that TRH stimulates respiratory discharge frequency by acting, presumably, on the pre-Bötzinger complex.
73. Sun Q-J, Pilowski P, Llewellyn-Smith IJ: Thyrotropin-releasing hormone inputs are preferentially directed towards respiratory motoneurons in rat nucleus ambiguus. J Comp A/euro/1996, 362:320-330. Using a combination of intracellular recordings, dye filling and immunohistochemistry, the authors demonstrate that respiratory motoneurons in the rostral nucleus ambiguus are preferentially innervated by TRH-immunoreactive boutons. Hypoglossal motoneurons received the fewest appositions from TRH-containing boutons.
74. Bayliss DA, Viana F, Kanter RK, Szymeczek-Seay CL, Berger AJ, Millhom DE: Early postnatal development of thyrotropinreleasing hormone (TRH) expression, TRH receptor binding, and TRH responses in neurons of rat brainstem. J Neurose/ 1994, 14:821-833.
75. Smith JC, Feldman JL: Central respiratory pattern generation studied in an in vitro mammalian brainstem-spinal cord preparation. In Respiratory Muscles and Their Neuromotor Control. Edited by Seick G, Gandevia SC, Cameron WE. New York: AR Liss; 1987:27-36.
76. Onimaru H, Arata A, Homma I: Firing properties of respiratory rhythm generating neurons in the absence of synaptic transmission in rat medulla in vitro. Exp Brain Res 1989, 76:530-536.
77. Hayashi F, Lipski J: The role of inhibitory amino acids in control of respiratory motor output in an arterially perfused rat Respir Physiol 1992, 89:47-63.
78. Paton JFR, Ramirez JM, Richter DW: Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats. Neurosci Lett 1994, 170:167-270.
79. Paton JFR, Richter DW: Role of fast inhibitory mechanisms in respiratory rhythm generation in the maturing mouse. J Physiol (Lond) 1995, 484:505-521.
80. Paton JFR, Richter DW: Maturational changes in the respiratory rhythm generator of the mouse. Pflugers Arch 1995, 430:114-124.
81. Klages S, Bellingham MC, Richter DW: Late expiratory inhibition of stage 2 expiratory neurons in the cat -a correlate of expiratory termination. J Neurophysiol 1993, 70:1307-1315.
82. Eugenin J: Generation of the respiratory rhythm: modelling the inspiratory off switch as a neural integrator. J Theor Biol 1995, 172:107-120.
83. Morrison SF, Cravo SL, Wilfehrt HM: Pontine lesions produce apneusis in the rat Brain Res 1994, 652:83-86.
84. Richter DW, Bischoff AM, Anders K, Bellingham M, Windhorst U: Response of the medullary respiratory network of the cat to hypoxia. J Physiol (Lond) 1991, 443:231-256.
85. England SJ, Melton JE, Douse MA, Duffm J: Activity of respiratory neurons during hypoxia in the chemodenervated cat J Appl Physiol 1995, 78:856-861. Demonstrates changes in the respiratory motor pattern during hypoxia The onset delay of late-inspiratory neurons decreases with respect to inspiratory phrenic nerve activity, and expiratory neurons cease firing before silence of the phrenic nerve.