1932

Abstract

Rhythmicity is a universal timing mechanism in the brain, and the rhythmogenic mechanisms are generally dynamic. This is illustrated for the neuronal control of breathing, a behavior that occurs as a one-, two-, or three-phase rhythm. Each breath is assembled stochastically, and increasing evidence suggests that each phase can be generated independently by a dedicated excitatory microcircuit. Within each microcircuit, rhythmicity emerges through three entangled mechanisms: () glutamatergic transmission, which is amplified by () intrinsic bursting and opposed by () concurrent inhibition. This rhythmogenic triangle is dynamically tuned by neuromodulators and other network interactions. The ability of coupled oscillators to reconfigure and recombine may allow breathing to remain robust yet plastic enough to conform to nonventilatory behaviors such as vocalization, swallowing, and coughing. Lessons learned from the respiratory network may translate to other highly dynamic and integrated rhythmic systems, if approached one breath at a time.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-080317-061756
2018-07-08
2024-06-25
Loading full text...

Full text loading...

/deliver/fulltext/neuro/41/1/annurev-neuro-080317-061756.html?itemId=/content/journals/10.1146/annurev-neuro-080317-061756&mimeType=html&fmt=ahah

Literature Cited

  1. Abdala AP, Toward MA, Dutschmann M, Bissonnette JM, Paton JF 2016. Deficiency of GABAergic synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome. J. Physiol. 594:223–37
    [Google Scholar]
  2. Alheid GF, McCrimmon DR 2008. The chemical neuroanatomy of breathing. Respir. Physiol. Neurobiol. 164:3–11
    [Google Scholar]
  3. Anderson TM, Garcia AJ 3rd, Baertsch NA, Pollak J, Bloom JC et al. 2016. A novel excitatory network for the control of breathing. Nature 536:76–80
    [Google Scholar]
  4. Anderson TM, Ramirez JM 2017. Respiratory rhythm generation: triple oscillator hypothesis. F1000Research 6:139
    [Google Scholar]
  5. Bacak BJ, Kim T, Smith JC, Rubin JE, Rybak IA 2016. Mixed-mode oscillations and population bursting in the pre-Bötzinger complex. eLife 5:e13403
    [Google Scholar]
  6. Ballantyne D, Andrzejewski M, Muckenhoff K, Scheid P 2004. Rhythms, synchrony and electrical coupling in the locus coeruleus. Respir. Physiol. Neurobiol. 143:199–214
    [Google Scholar]
  7. Bonis JM, Neumueller SE, Marshall BD, Krause KL, Qian B et al. 2011. The effects of lesions in the dorsolateral pons on the coordination of swallowing and breathing in awake goats. Respir. Physiol. Neurobiol. 175:272–82
    [Google Scholar]
  8. Bouvier J, Thoby-Brisson M, Renier N, Dubreuil V, Ericson J et al. 2010. Hindbrain interneurons and axon guidance signaling critical for breathing. Nat. Neurosci. 13:1066–74
    [Google Scholar]
  9. Brunel N, Chance FS, Fourcaud N, Abbott LF 2001. Effects of synaptic noise and filtering on the frequency response of spiking neurons. Phys. Rev. Lett. 86:2186–89
    [Google Scholar]
  10. Burke PG, Abbott SB, Coates MB, Viar KE, Stornetta RL, Guyenet PG 2014. Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent cardiorespiratory stimulation and arousal with sighs in rats. Am. J. Respir. Crit. Care Med. 190:1301–10
    [Google Scholar]
  11. Burkitt AN 2006. A review of the integrate-and-fire neuron model: I. Homogeneous synaptic input. Biol. Cybern. 95:1–19
    [Google Scholar]
  12. Buzsáki G, Moser EI 2013. Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nat. Neurosci. 16:130–38
    [Google Scholar]
  13. Buzsáki G, Schomburg EW 2015. What does gamma coherence tell us about inter-regional neural communication. Nat. Neurosci. 18:484–89
    [Google Scholar]
  14. Bywalez W, Menegazzi P, Rieger D, Schmid B, Helfrich-Förster C, Yoshii T 2012. The dual-oscillator system of Drosophila melanogaster under natural-like temperature cycles. Chronobiol. Int. 29:395–407
    [Google Scholar]
  15. Cangiano L, Hill RH, Grillner S 2012. The hemisegmental locomotor network revisited. Neuroscience 210:33–37
    [Google Scholar]
  16. Carroll MS, Ramirez JM 2013. Cycle-by-cycle assembly of respiratory network activity is dynamic and stochastic. J. Neurophysiol. 109:296–305
    [Google Scholar]
  17. Carroll MS, Viemari JC, Ramirez JM 2013. Patterns of inspiratory phase-dependent activity in the in vitro respiratory network. J. Neurophysiol. 109:285–95
    [Google Scholar]
  18. Chagnac-Amitai Y, Connors BW 1989. Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. J. Neurophysiol. 62:1149–62
    [Google Scholar]
  19. Chance FS, Abbott LF, Reyes AD 2002. Gain modulation from background synaptic input. Neuron 35:773–82
    [Google Scholar]
  20. Chen L, Zhang J, Ding Y, Li H, Nie L et al. 2013. KATP channels of parafacial respiratory group (pFRG) neurons are involved in H2S-mediated central inhibition of respiratory rhythm in medullary slices of neonatal rats. Brain Res 1527:141–48
    [Google Scholar]
  21. Cheron G, Márquez-Ruiz J, Dan B 2016. Oscillations, timing, plasticity, and learning in the cerebellum. Cerebellum 15:122–38
    [Google Scholar]
  22. Cui Y, Kam K, Sherman D, Janczewski WA, Zheng Y, Feldman JL 2016. Defining preBötzinger complex rhythm- and pattern-generating neural microcircuits in vivo. Neuron 91:602–14
    [Google Scholar]
  23. Del Negro CA, Koshiya N, Butera RJ Jr, Smith JC 2002. Persistent sodium current, membrane properties and bursting behavior of pre-Bötzinger complex inspiratory neurons in vitro. J. Neurophysiol. 88:2242–50
    [Google Scholar]
  24. Deschênes M, Takatoh J, Kurnikova A, Moore JD, Demers M et al. 2016. Inhibition, not excitation, drives rhythmic whisking. Neuron 90:374–87
    [Google Scholar]
  25. Destexhe A, Rudolph M, Pare D 2003. The high-conductance state of neocortical neurons in vivo. Nat. Rev. Neurosci. 4:739–51
    [Google Scholar]
  26. Dhingra RR, Dutschmann M, Dick TE 2016. Blockade of dorsolateral pontine 5HT1A receptors destabilizes the respiratory rhythm in C57BL6/J wild-type mice. Respir. Physiol. Neurobiol. 226:110–14
    [Google Scholar]
  27. Dhingra RR, Dutschmann M, Galán RF, Dick TE 2017. Kölliker-Fuse nuclei regulate respiratory rhythm variability via a gain-control mechanism. Am. J. Physiol. Regul. Integr. Comp. Physiol. 312:R172–88
    [Google Scholar]
  28. Dogas Z, Krolo M, Stuth EA, Tonkovic-Capin M, Hopp FA et al. 1998. Differential effects of GABAA receptor antagonists in the control of respiratory neuronal discharge patterns. J. Neurophysiol. 80:2368–77
    [Google Scholar]
  29. Doi A, Ramirez JM 2008. Neuromodulation and the orchestration of the respiratory rhythm. Respir. Physiol. Neurobiol. 164:96–104
    [Google Scholar]
  30. Dubois M, Chenivesse C, Raux M, Morales-Robles A, Nierat MC et al. 2016. Neurophysiological evidence for a cortical contribution to the wakefulness-related drive to breathe explaining hypocapnia-resistant ventilation in humans. J. Neurosci. 36:10673–82
    [Google Scholar]
  31. Dutschmann M, Jones SE, Subramanian HH, Stanic D, Bautista TG 2014. The physiological significance of postinspiration in respiratory control. Prog. Brain Res. 212:113–30
    [Google Scholar]
  32. Earhart GM, Stein PS 2000. Step, swim, and scratch motor patterns in the turtle. J. Neurophysiol. 84:2181–90
    [Google Scholar]
  33. English DF, Peyrache A, Stark E, Roux L, Vallentin D et al. 2014. Excitation and inhibition compete to control spiking during hippocampal ripples: intracellular study in behaving mice. J. Neurosci. 34:16509–17
    [Google Scholar]
  34. Etheredge JA, Murchison D, Abbott LC, Griffith WH 2007. Functional compensation by other voltage-gated Ca2+ channels in mouse basal forebrain neurons with CaV2.1 mutations. Brain Res 1140:105–19
    [Google Scholar]
  35. Eugenin J, Nicholls JG, Cohen LB, Muller KJ 2006. Optical recording from respiratory pattern generator of fetal mouse brainstem reveals a distributed network. Neuroscience 137:1221–27
    [Google Scholar]
  36. Feldman JL, Del Negro CA, Gray PA 2013. Understanding the rhythm of breathing: so near, yet so far. Annu. Rev. Physiol. 75:423–52
    [Google Scholar]
  37. Feldman JL, Kam K 2015. Facing the challenge of mammalian neural microcircuits: Taking a few breaths may help. J. Physiol. 593:3–23
    [Google Scholar]
  38. Forster H, Bonis J, Krause K, Wenninger J, Neumueller S et al. 2014. Contributions of the pre-Bötzinger complex and the Kölliker-Fuse nuclei to respiratory rhythm and pattern generation in awake and sleeping goats. Prog. Brain Res. 209:73–89
    [Google Scholar]
  39. Frigon A 2009. Reconfiguration of the spinal interneuronal network during locomotion in vertebrates. J. Neurophysiol. 101:2201–3
    [Google Scholar]
  40. Garcia AJ 3rd, Dashevskiy T, Khuu MA, Ramirez JM 2017. Chronic intermittent hypoxia differentially impacts different states of inspiratory activity at the level of the preBötzinger complex. Front Physiol 8:571
    [Google Scholar]
  41. Garcia AJ 3rd, Zanella S, Dashevskiy T, Khan SA, Khuu MA et al. 2016. Chronic intermittent hypoxia alters local respiratory circuit function at the level of the preBötzinger complex. Front. Neurosci. 10:4
    [Google Scholar]
  42. Golowasch J 2014. Ionic current variability and functional stability in the nervous system. Bioscience 64:570–80
    [Google Scholar]
  43. Grashow R, Brookings T, Marder E 2010. Compensation for variable intrinsic neuronal excitability by circuit-synaptic interactions. J. Neurosci. 30:9145–56
    [Google Scholar]
  44. Gray PA, Hayes JA, Ling GY, Llona I, Tupal S et al. 2010. Developmental origin of preBötzinger complex respiratory neurons. J. Neurosci. 30:14883–95
    [Google Scholar]
  45. Gray PA, Janczewski WA, Mellen N, McCrimmon DR, Feldman JL 2001. Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons. Nat. Neurosci. 4:927–30
    [Google Scholar]
  46. Grillner S, El Manira A 2015. The intrinsic operation of the networks that make us locomote. Curr. Opin. Neurobiol. 31:244–49
    [Google Scholar]
  47. Guyenet PG, Bayliss DA, Stornetta RL, Fortuna MG, Abbott SB, DePuy SD 2009. Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity. Respir. Physiol. Neurobiol. 168:59–68
    [Google Scholar]
  48. Haedo RJ, Golowasch J 2006. Ionic mechanism underlying recovery of rhythmic activity in adult isolated neurons. J. Neurophysiol. 96:1860–76
    [Google Scholar]
  49. Hamood AW, Marder E 2014. Animal-to-animal variability in neuromodulation and circuit function. Cold Spring Harb. Symp. Quant. Biol. 79:21–28
    [Google Scholar]
  50. Harris KD, Dashevskiy T, Mendoza J, Garcia AJ 3rd, Ramirez JM, Shea-Brown E 2017. Different roles for inhibition in the rhythm-generating respiratory network. J. Neurophysiol. 118:2070–88
    [Google Scholar]
  51. Hayes JA, Kottick A, Picardo MCD, Halleran AD, Smith RD et al. 2017. Transcriptome of neonatal preBötzinger complex neurones in Dbx1 reporter mice. Sci. Rep. 7:8669
    [Google Scholar]
  52. Hernandez-Miranda LR, Ruffault PL, Bouvier JC, Murray AJ, Morin-Surun MP et al. 2017. Genetic identification of a hindbrain nucleus essential for innate vocalization. PNAS 114:8095–100
    [Google Scholar]
  53. Huckstepp RT, Cardoza KP, Henderson LE, Feldman JL 2015. Role of parafacial nuclei in control of breathing in adult rats. J. Neurosci. 35:1052–67
    [Google Scholar]
  54. Huckstepp RT, Henderson LE, Cardoza KP, Feldman JL 2016. Interactions between respiratory oscillators in adult rats. eLife 5:e14203
    [Google Scholar]
  55. Im SH, Taghert PH 2010. PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila. J. Comp. Neurol 518:1925–45
    [Google Scholar]
  56. Janczewski WA, Feldman JL 2006. Distinct rhythm generators for inspiration and expiration in the juvenile rat. J. Physiol. 570:407–20
    [Google Scholar]
  57. Janczewski WA, Tashima A, Hsu P, Cui Y, Feldman JL 2013. Role of inhibition in respiratory pattern generation. J. Neurosci. 33:5454–65
    [Google Scholar]
  58. Jenkin SE, Milsom WK 2014. Expiration: breathing's other face. Prog. Brain Res. 212:131–47
    [Google Scholar]
  59. Jenkin SE, Milsom WK, Zoccal DB 2017. The Kölliker-Fuse nucleus acts as a timekeeper for late-expiratory abdominal activity. Neuroscience 348:63–72
    [Google Scholar]
  60. Jessberger J, Zhong W, Brankack J, Draguhn A 2016. Olfactory bulb field potentials and respiration in sleep-wake states of mice. Neural Plast 2016:4570831
    [Google Scholar]
  61. Jing J, Vilim FS, Horn CC, Alexeeva V, Hatcher NG et al. 2007. From hunger to satiety: reconfiguration of a feeding network by Aplysia neuropeptide Y. J. Neurosci. 27:3490–502
    [Google Scholar]
  62. Kam K, Worrell JW, Janczewski WA, Cui Y, Feldman JL 2013a. Distinct inspiratory rhythm and pattern generating mechanisms in the preBötzinger complex. J. Neurosci. 33:9235–45
    [Google Scholar]
  63. Kam K, Worrell JW, Ventalon C, Emiliani V, Feldman JL 2013b. Emergence of population bursts from simultaneous activation of small subsets of preBötzinger complex inspiratory neurons. J. Neurosci. 33:3332–38
    [Google Scholar]
  64. Katz PS 2016. Evolution of central pattern generators and rhythmic behaviours. Philos. Trans. R. Soc. B 371:20150057
    [Google Scholar]
  65. Kay LM, Lazzara P 2010. How global are olfactory bulb oscillations. J. Neurophysiol. 104:1768–73
    [Google Scholar]
  66. Kleinfeld D, Moore JD, Wang F, Deschênes M 2014. The brainstem oscillator for whisking and the case for breathing as the master clock for orofacial motor actions. Cold Spring Harb. Symp. Quant. Biol. 79:29–39
    [Google Scholar]
  67. Koch H, Garcia AJ 3rd, Ramirez JM 2011. Network reconfiguration and neuronal plasticity in rhythm-generating networks. Integr. Comp. Biol. 51:856–68
    [Google Scholar]
  68. Koch H, Zanella S, Elsen GE, Smith L, Doi A et al. 2013. Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels. J. Neurosci. 33:3633–45
    [Google Scholar]
  69. Kolind J, Hounsgaard J, Berg RW 2012. Opposing effects of intrinsic conductance and correlated synaptic input on Vm-fluctuations during network activity. Front. Comput. Neurosci. 6:40
    [Google Scholar]
  70. Kottick A, Martin CA, Del Negro CA 2017. Fate mapping neurons and glia derived from Dbx1-expressing progenitors in mouse preBötzinger complex. Physiol. Rep. 5:e13300
    [Google Scholar]
  71. Krause KL, Forster HV, Kiner T, Davis SE, Bonis JM et al. 2009. Normal breathing pattern and arterial blood gases in awake and sleeping goats after near total destruction of the presumed pre-Bötzinger complex and the surrounding region. J. Appl. Physiol. 106:605–19
    [Google Scholar]
  72. Lee ML, Swanson BE, de la Iglesia HO 2009. Circadian timing of REM sleep is coupled to an oscillator within the dorsomedial suprachiasmatic nucleus. Curr. Biol. 19:848–52
    [Google Scholar]
  73. Li P, Janczewski WA, Yackle K, Kam K, Pagliardini S et al. 2016. The peptidergic control circuit for sighing. Nature 530:293–97
    [Google Scholar]
  74. Li WC 2015. Selective gating of neuronal activity by intrinsic properties in distinct motor rhythms. J. Neurosci. 35:9799–810
    [Google Scholar]
  75. Liao JC, Fetcho JR 2008. Shared versus specialized glycinergic spinal interneurons in axial motor circuits of larval zebrafish. J. Neurosci. 28:12982–92
    [Google Scholar]
  76. Lieske SP, Thoby-Brisson M, Telgkamp P, Ramirez JM 2000. Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps. Nat. Neurosci. 3:600–7
    [Google Scholar]
  77. Lindsey BG, Morris KF, Shannon R, Gerstein GL 1997. Repeated patterns of distributed synchrony in neuronal assemblies. J. Neurophysiol. 78:1714–19
    [Google Scholar]
  78. Lockmann AL, Laplagne DA, Leao RN, Tort AB 2016. A respiration-coupled rhythm in the rat hippocampus independent of theta and slow oscillations. J. Neurosci. 36:5338–52
    [Google Scholar]
  79. Marchenko V, Koizumi H, Mosher B, Koshiya N, Tariq MF et al. 2016. Perturbations of respiratory rhythm and pattern by disrupting synaptic inhibition within pre-Bötzinger and Bötzinger complexes. eNeuro 3:0011–16 2016.
    [Google Scholar]
  80. Masaoka Y, Izumizaki M, Homma I 2014. Where is the rhythm generator for emotional breathing. Prog. Brain Res. 209:367–77
    [Google Scholar]
  81. McCormick DA, McGinley MJ, Salkoff DB 2015. Brain state dependent activity in the cortex and thalamus. Curr. Opin. Neurobiol. 31:133–40
    [Google Scholar]
  82. McCrimmon DR, Ramirez JM, Alford S, Zuperku EJ 2000. Unraveling the mechanism for respiratory rhythm generation. Bioessays 22:6–9
    [Google Scholar]
  83. McKay LC, Feldman JL 2008. Unilateral ablation of pre-Bötzinger complex disrupts breathing during sleep but not wakefulness. Am. J. Respir. Crit. Care Med. 178:89–95
    [Google Scholar]
  84. Medina-Martínez JS, Greising SM, Sieck GC, Mantilla CB 2015. Semi-automated assessment of transdiaphragmatic pressure variability across motor behaviors. Respir. Physiol. Neurobiol. 215:73–81
    [Google Scholar]
  85. Mellen NM 2010. Degeneracy as a substrate for respiratory regulation. Respir. Physiol. Neurobiol. 172:1–7
    [Google Scholar]
  86. Mellen NM, Mishra D 2010. Functional anatomical evidence for respiratory rhythmogenic function of endogenous bursters in rat medulla. J. Neurosci. 30:8383–92
    [Google Scholar]
  87. Mendoza G, Merchant H 2014. Motor system evolution and the emergence of high cognitive functions. Prog. Neurobiol. 122:73–93
    [Google Scholar]
  88. Morgado-Valle C, Baca SM, Feldman JL 2010. Glycinergic pacemaker neurons in preBötzinger complex of neonatal mouse. J. Neurosci. 30:3634–39
    [Google Scholar]
  89. Morris KF, Shannon R, Lindsey BG 2001. Changes in cat medullary neurone firing rates and synchrony following induction of respiratory long-term facilitation. J. Physiol. 532:483–97
    [Google Scholar]
  90. Nguyen Chi V, Müller C, Wolfenstetter T, Yanovsky Y, Draguhn A et al. 2016. Hippocampal respiration-driven rhythm distinct from theta oscillations in awake mice. J. Neurosci. 36:162–77
    [Google Scholar]
  91. Nieto-Posadas A, Flores-Martínez E, Lorea-Hernández JJ, Rivera-Angulo AJ, Pérez-Ortega JE et al. 2014. Change in network connectivity during fictive-gasping generation in hypoxia: prevention by a metabolic intermediate. Front. Physiol. 5:265
    [Google Scholar]
  92. Oke Y, Boiroux D, Miwakeichi F, Oku Y 2015. Stochastic activation among inspiratory cells in the pre-Bötzinger complex of the rat medulla revealed by Ca2+ imaging. Neurosci. Lett. 595:12–17
    [Google Scholar]
  93. O'Leary T, Williams AH, Caplan JS, Marder E 2013. Correlations in ion channel expression emerge from homeostatic tuning rules. PNAS 110:E2645–54
    [Google Scholar]
  94. O'Leary T, Williams AH, Franci A, Marder E 2014. Cell types, network homeostasis, and pathological compensation from a biologically plausible ion channel expression model. Neuron 82:809–21
    [Google Scholar]
  95. Olypher AV, Calabrese RL 2007. Using constraints on neuronal activity to reveal compensatory changes in neuronal parameters. J. Neurophysiol. 98:3749–58
    [Google Scholar]
  96. Onimaru H, Ikeda K, Kawakami K 2009. Phox2b, RTN/pFRG neurons and respiratory rhythmogenesis. Respir. Physiol. Neurobiol. 168:13–18
    [Google Scholar]
  97. Orem J, Trotter RH 1992. Postinspiratory neuronal activities during behavioral control, sleep, and wakefulness. J. Appl. Physiol. 72:2369–77
    [Google Scholar]
  98. Pagliardini S, Janczewski WA, Tan W, Dickson CT, Deisseroth K, Feldman JL 2011. Active expiration induced by excitation of ventral medulla in adult anesthetized rats. J. Neurosci. 31:2895–905
    [Google Scholar]
  99. Paton JF, Abdala AP, Koizumi H, Smith JC, St-John WM 2006. Respiratory rhythm generation during gasping depends on persistent sodium current. Nat. Neurosci. 9:311–13
    [Google Scholar]
  100. Pearce RA, Stornetta RL, Guyenet PG 1989. Retrotrapezoid nucleus in the rat. Neurosci. Lett. 101:138–42
    [Google Scholar]
  101. Peña F, Parkis MA, Tryba AK, Ramirez JM 2004. Differential contribution of pacemaker properties to the generation of respiratory rhythms during normoxia and hypoxia. Neuron 43:105–17
    [Google Scholar]
  102. Peña F, Ramirez JM 2004. Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network. J. Neurosci. 24:7549–56
    [Google Scholar]
  103. Peng YJ, Zhang X, Gridina A, Chupikova I, McCormick DL et al. 2017. Complementary roles of gasotransmitters CO and H2S in sleep apnea. PNAS 114:1413–18
    [Google Scholar]
  104. Petersen PC, Vestergaard M, Jensen KH, Berg RW 2014. Premotor spinal network with balanced excitation and inhibition during motor patterns has high resilience to structural division. J. Neurosci. 34:2774–84
    [Google Scholar]
  105. Picardo MC, Weragalaarachchi KT, Akins VT, Del Negro CA 2013. Physiological and morphological properties of Dbx1-derived respiratory neurons in the pre-Bötzinger complex of neonatal mice. J. Physiol. 591:2687–703
    [Google Scholar]
  106. Pitts T, Morris K, Lindsey B, Davenport P, Poliacek I, Bolser D 2012. Co-ordination of cough and swallow in vivo and in silico. Exp. Physiol. 97:469–73
    [Google Scholar]
  107. Prinz AA 2017. Degeneracy rules!. J. Physiol 595:2409
    [Google Scholar]
  108. Radna RJ, MacLean PD 1981. Vagal elicitation of respiratory-type and other unit responses in basal limbic structures of squirrel monkeys. Brain Res 213:45–61
    [Google Scholar]
  109. Ramirez JM 1998. Reconfiguration of the respiratory network at the onset of locust flight. J. Neurophysiol. 80:3137–47
    [Google Scholar]
  110. Ramirez JM 2014. The integrative role of the sigh in psychology, physiology, pathology, and neurobiology. Prog. Brain Res. 209:91–129
    [Google Scholar]
  111. Ramirez JM, Dashevskiy T, Marlin IA, Baertsch N 2016. Microcircuits in respiratory rhythm generation: commonalities with other rhythm generating networks and evolutionary perspectives. Curr. Opin. Neurobiol. 41:53–61
    [Google Scholar]
  112. Ramirez JM, Doi A, Garcia AJ 3rd, Elsen FP, Koch H, Wei AD 2012. The cellular building blocks of breathing. Compr. Physiol. 2:2683–731
    [Google Scholar]
  113. Ramirez JM, Garcia AJ 3rd, Anderson TM, Koschnitzky JE, Peng YJ et al. 2013. Central and peripheral factors contributing to obstructive sleep apneas. Respir. Physiol. Neurobiol. 189:344–53
    [Google Scholar]
  114. Ramirez JM, Lieske SP 2003. Commentary on the definition of eupnea and gasping. Respir. Physiol. Neurobiol. 139:113–19
    [Google Scholar]
  115. Ramirez JM, Quellmalz UJ, Richter DW 1996. Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice. J. Physiol. 491:Pt. 3799–812
    [Google Scholar]
  116. Ramirez JM, Quellmalz UJ, Wilken B, Richter DW 1998a. The hypoxic response of neurones within the in vitro mammalian respiratory network. J. Physiol. 507:Pt. 2571–82
    [Google Scholar]
  117. Ramirez JM, Richter DW 1996. The neuronal mechanisms of respiratory rhythm generation. Curr. Opin. Neurobiol. 6:817–25
    [Google Scholar]
  118. Ramirez JM, Schwarzacher SW, Pierrefiche O, Olivera BM, Richter DW 1998b. Selective lesioning of the cat pre-Bötzinger complex in vivo eliminates breathing but not gasping. J. Physiol. 507:Pt. 3895–907
    [Google Scholar]
  119. Ramirez JM, Tryba AK, Peña F 2004. Pacemaker neurons and neuronal networks: an integrative view. Curr. Opin. Neurobiol. 14:665–74
    [Google Scholar]
  120. Ramirez JM, Viemari JC 2005. Determinants of inspiratory activity. Respir. Physiol. Neurobiol. 147:145–57
    [Google Scholar]
  121. Revill AL, Vann NC, Akins VT, Kottick A, Gray PA et al. 2015. Dbx1 precursor cells are a source of inspiratory XII premotoneurons. eLife 4:e12301
    [Google Scholar]
  122. Richter DW, Bischoff A, Anders K, Bellingham M, Windhorst U 1991. Response of the medullary respiratory network of the cat to hypoxia. J. Physiol. 443:231–56
    [Google Scholar]
  123. Richter DW, Smith JC 2014. Respiratory rhythm generation in vivo. Physiology 29:58–71
    [Google Scholar]
  124. Rojas-Libano D, Frederick DE, Egaña JI, Kay LM 2014. The olfactory bulb theta rhythm follows all frequencies of diaphragmatic respiration in the freely behaving rat. Front. Behav. Neurosci. 8:214
    [Google Scholar]
  125. Rotstein HG, Olarinre M, Golowasch J 2016. Dynamic compensation mechanism gives rise to period and duty-cycle level sets in oscillatory neuronal models. J. Neurophysiol. 116:2431–52
    [Google Scholar]
  126. Rudolph M, Pelletier JG, Pare D, Destexhe A 2005. Characterization of synaptic conductances and integrative properties during electrically induced EEG-activated states in neocortical neurons in vivo. J. Neurophysiol. 94:2805–21
    [Google Scholar]
  127. Schreihofer AM, Stornetta RL, Guyenet PG 1999. Evidence for glycinergic respiratory neurons: Bötzinger neurons express mRNA for glycinergic transporter 2. J. Comp. Neurol. 407:583–97
    [Google Scholar]
  128. Schwarzacher SW, Rüb U, Deller T 2011. Neuroanatomical characteristics of the human pre-Bötzinger complex and its involvement in neurodegenerative brainstem diseases. Brain 134:24–35
    [Google Scholar]
  129. Schwindt P, Crill W 1999. Mechanisms underlying burst and regular spiking evoked by dendritic depolarization in layer 5 cortical pyramidal neurons. J. Neurophysiol. 81:1341–54
    [Google Scholar]
  130. Segers LS, Nuding SC, Vovk A, Pitts T, Baekey DM et al. 2012. Discharge identity of medullary inspiratory neurons is altered during repetitive fictive cough. Front. Physiol. 3:223
    [Google Scholar]
  131. Shadlen MN, Newsome WT 1998. The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J. Neurosci. 18:3870–96
    [Google Scholar]
  132. Shannon R, Baekey DM, Morris KF, Li Z, Lindsey BG 2000. Functional connectivity among ventrolateral medullary respiratory neurones and responses during fictive cough in the cat. J. Physiol. 525:Pt. 1207–24
    [Google Scholar]
  133. Shao XM, Feldman JL 1997. Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and GABAergic neural transmission. J. Neurophysiol. 77:1853–60
    [Google Scholar]
  134. Shu Y, Hasenstaub A, McCormick DA 2003. Turning on and off recurrent balanced cortical activity. Nature 423:288–93
    [Google Scholar]
  135. Silva JN, Tanabe FM, Moreira TS, Takakura AC 2016. Neuroanatomical and physiological evidence that the retrotrapezoid nucleus/parafacial region regulates expiration in adult rats. Respir. Physiol. Neurobiol. 227:9–22
    [Google Scholar]
  136. Smith JC, Abdala AP, Borgmann A, Rybak IA, Paton JF 2013. Brainstem respiratory networks: building blocks and microcircuits. Trends Neurosci 36:152–62
    [Google Scholar]
  137. Smith JC, Abdala AP, Koizumi H, Rybak IA, Paton JF 2007. Spatial and functional architecture of the mammalian brain stem respiratory network: a hierarchy of three oscillatory mechanisms. J. Neurophysiol. 98:3370–87
    [Google Scholar]
  138. Smith JC, Abdala AP, Rybak IA, Paton JF 2009. Structural and functional architecture of respiratory networks in the mammalian brainstem. Philos. Trans. R. Soc. B 364:2577–87
    [Google Scholar]
  139. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL 1991. Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254:726–29
    [Google Scholar]
  140. Soffe SR 1993. Two distinct rhythmic motor patterns are driven by common premotor and motor neurons in a simple vertebrate spinal cord. J. Neurosci. 13:4456–69
    [Google Scholar]
  141. St-John WM 1998. Neurogenesis of patterns of automatic ventilatory activity. Prog. Neurobiol. 56:97–117
    [Google Scholar]
  142. Stornetta RL, Moreira TS, Takakura AC, Kang BJ, Chang DA et al. 2006. Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. J. Neurosci. 26:10305–14
    [Google Scholar]
  143. Stuart G, Sakmann B 1995. Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons. Neuron 15:1065–76
    [Google Scholar]
  144. Subramanian HH, Arun M, Silburn PA, Holstege G 2016. Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray. J. Comp. Neurol. 524:1540–57
    [Google Scholar]
  145. Swensen AM, Bean BP 2005. Robustness of burst firing in dissociated Purkinje neurons with acute or long-term reductions in sodium conductance. J. Neurosci. 25:3509–20
    [Google Scholar]
  146. Tan W, Janczewski WA, Yang P, Shao XM, Callaway EM, Feldman JL 2008. Silencing preBötzinger complex somatostatin-expressing neurons induces persistent apnea in awake rat. Nat. Neurosci. 11:538–40
    [Google Scholar]
  147. Tan W, Sherman D, Turesson J, Shao XM, Janczewski WA, Feldman JL 2012. Reelin demarcates a subset of pre-Bötzinger complex neurons in adult rat. J. Comp. Neurol. 520:606–19
    [Google Scholar]
  148. Temporal S, Desai M, Khorkova O, Varghese G, Dai A et al. 2012. Neuromodulation independently determines correlated channel expression and conductance levels in motor neurons of the stomatogastric ganglion. J. Neurophysiol. 107:718–27
    [Google Scholar]
  149. Thoby-Brisson M, Ramirez JM 2001. Identification of two types of inspiratory pacemaker neurons in the isolated respiratory neural network of mice. J. Neurophysiol. 86:104–12
    [Google Scholar]
  150. Tryba AK, Peña F, Ramirez JM 2003. Stabilization of bursting in respiratory pacemaker neurons. J. Neurosci. 23:3538–46
    [Google Scholar]
  151. Tryba AK, Ramirez JM 2004. Background sodium current stabilizes bursting in respiratory pacemaker neurons. J. Neurobiol. 60:481–89
    [Google Scholar]
  152. Tsanov M, Chah E, Reilly R, O'Mara SM 2014. Respiratory cycle entrainment of septal neurons mediates the fast coupling of sniffing rate and hippocampal theta rhythm. Eur. J. Neurosci. 39:957–74
    [Google Scholar]
  153. Tupal S, Huang WH, Picardo MC, Ling GY, Del Negro CA et al. 2014. Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice. eLife 3:e02265
    [Google Scholar]
  154. van Drongelen W, Koch H, Elsen FP, Lee HC, Mrejeru A et al. 2006. Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro. J. Neurophysiol. 96:2564–77
    [Google Scholar]
  155. van Drongelen W, Koch H, Marcuccilli C, Peña F, Ramirez JM 2003. Synchrony levels during evoked seizure-like bursts in mouse neocortical slices. J. Neurophysiol. 90:1571–80
    [Google Scholar]
  156. van Vreeswijk C, Sompolinsky H 1996. Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science 274:1724–26
    [Google Scholar]
  157. Viemari JC, Ramirez JM 2006. Norepinephrine differentially modulates different types of respiratory pacemaker and nonpacemaker neurons. J. Neurophysiol. 95:2070–82
    [Google Scholar]
  158. Viemari JC, Roux JC, Tryba AK, Saywell V, Burnet H et al. 2005. Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J. Neurosci. 25:11521–30
    [Google Scholar]
  159. Wang X, Hayes JA, Revill AL, Song H, Kottick A et al. 2014. Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice. eLife 3:e03427
    [Google Scholar]
  160. Watson AH, Williams C, James BV 2012. Activity patterns in latissimus dorsi and sternocleidomastoid in classical singers. J. Voice 26:e95–105
    [Google Scholar]
  161. Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Ramirez JM 2008. Autonomic dysregulation in young girls with Rett syndrome during nighttime in-home recordings. Pediatr. Pulmonol. 43:1045–60
    [Google Scholar]
  162. Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL et al. 2006. Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr. Res. 60:443–49
    [Google Scholar]
  163. Weimann JM, Meyrand P, Marder E 1991. Neurons that form multiple pattern generators: identification and multiple activity patterns of gastric/pyloric neurons in the crab stomatogastric system. J. Neurophysiol. 65:111–22
    [Google Scholar]
  164. Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J et al. 2004. Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats. J. Appl. Physiol. 97:1629–36
    [Google Scholar]
  165. White RS, Nusbaum MP 2011. The same core rhythm generator underlies different rhythmic motor patterns. J. Neurosci. 31:11484–94
    [Google Scholar]
  166. Winter SM, Fresemann J, Schnell C, Oku Y, Hirrlinger J, Hulsmann S 2009. Glycinergic interneurons are functionally integrated into the inspiratory network of mouse medullary slices. Pflugers Arch 458:459–69
    [Google Scholar]
  167. Yackle K, Schwarz LA, Kam K, Sorokin JM, Huguenard JR et al. 2017. Breathing control center neurons that promote arousal in mice. Science 355:1411–15
    [Google Scholar]
  168. Yarom Y, Hounsgaard J 2011. Voltage fluctuations in neurons: signal or noise. Physiol. Rev. 91:917–29
    [Google Scholar]
  169. Zanella S, Doi A, Garcia AJ 3rd, Elsen F, Kirsch S et al. 2014. When norepinephrine becomes a driver of breathing irregularities: how intermittent hypoxia fundamentally alters the modulatory response of the respiratory network. J. Neurosci. 34:36–50
    [Google Scholar]
  170. Zelano C, Jiang H, Zhou G, Arora N, Schuele S et al. 2016. Nasal respiration entrains human limbic oscillations and modulates cognitive function. J. Neurosci. 36:12448–67
    [Google Scholar]
  171. Zheng N, Raman IM 2011. Prolonged postinhibitory rebound firing in the cerebellar nuclei mediated by group I metabotropic glutamate receptor potentiation of l-type calcium currents. J. Neurosci. 31:10283–92
    [Google Scholar]
  172. Zhong W, Ciatipis M, Wolfenstetter T, Jessberger J, Müller C et al. 2017. Selective entrainment of gamma subbands by different slow network oscillations. PNAS 114:4519–24
    [Google Scholar]
  173. Zuperku EJ, Stucke AG, Hopp FA, Stuth EA 2017. Characteristics of breathing rate control mediated by a subregion within the pontine parabrachial complex. J. Neurophysiol. 117:1030–42
    [Google Scholar]
/content/journals/10.1146/annurev-neuro-080317-061756
Loading
/content/journals/10.1146/annurev-neuro-080317-061756
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error