Interacting oscillations in neural control of breathing: modeling and qualitative analysis
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In mammalian respiration, late-expiratory (late-E, or pre-inspiratory) oscillations emerge in abdominal motor output with increasing metabolic demands (e.g., during hypercapnia, hypoxia, etc.). These oscillations originate in the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and couple with the respiratory oscillations generated by the interacting neural populations of the Bötzinger (BötC) and pre-Bötzinger (pre-BötC) complexes, representing the kernel of the respiratory central pattern generator. Recently, we analyzed experimental data on the generation of late-E oscillations and proposed a large-scale computational model that simulates the possible interactions between the BötC/pre-BötC and RTN/pFRG oscillations under different conditions. Here we describe a reduced model that maintains the essential features and architecture of the large-scale model, but relies on simplified activity-based descriptions of neural populations. This simplification allowed us to use methods of dynamical systems theory, such as fast-slow decomposition, bifurcation analysis, and phase plane analysis, to elucidate the mechanisms and dynamics of synchronization between the RTN/pFRG and BötC/pre-BötC oscillations. Three physiologically relevant behaviors have been analyzed: emergence and quantal acceleration of late-E oscillations during hypercapnia, transformation of the late-E activity into a biphasic-E activity during hypercapnic hypoxia, and quantal slowing of BötC/pre-BötC oscillations with the reduction of pre-BötC excitability. Each behavior is elicited by gradual changes in excitatory drives or other model parameters, reflecting specific changes in metabolic and/or physiological conditions. Our results provide important theoretical insights into interactions between RTN/pFRG and BötC/pre-BötC oscillations and the role of these interactions in the control of breathing under different metabolic conditions.
KeywordsNeural oscillations Respiratory central pattern generator Pre-Bötzinger Complex Parafacial respiratory group Coupled oscillators Phase plane analysis
This study was supported by National Institute of Neurological Disorders and Stroke (NINDS), NIH grant R01 NS057815 (I.A. Rybak), NSF grant DMS 0716936 (J. E. Rubin) and in part by the Intramural Research Program of the NIH, NINDS (J.C. Smith).
- Burke, P. G., Abbott, S. B., McMullan, S., Goodchild, A. K., & Pilowsky, P. M. (2010). Somatostatin selectively ablates post-inspiratory activity after injection into the Bötzinger complex. Neuroscience, 167, 528–539.Google Scholar
- Feldman, J. L. (1986). Neurophysiology of breathing in mammals. In F. E. Bloom (Ed.), Handbook of physiology (Vol. 4, pp. 463–524). Bethesda, MD: Am Physiol SocGoogle Scholar
- Fortin, G., & Thoby-Brisson, M. (2009). Embryonic emergence of the respiratory rhythm generator. Respiratory Physiology & Neurobiology, 168, 86–91.Google Scholar
- Guyenet, P. G. & Mulkey, D. K. (2010). Retrotrapezoid nucleus and parafacial respiratory group. Respir Physiol Neurobiol (Epub ahead of print, Feb 25).Google Scholar
- Izhikevich E. M. (2007). Dynamical Systems in Neuroscience: The Geometry of Excitability and Bursting. The MIT PressGoogle Scholar
- Janczewski, W. A., & Feldman, J. L. (2006a). Distinct rhythm generators for inspiration and expiration in the juvenile rat. Journal of Physiology-London, 570(2), 407–420.Google Scholar
- Joseph, I. M., & Butera, R. J. (2005). A simple model of dynamic interactions between respiratory centers. Conference Proceedings IEEE Engineering in Medicine & Biology Society, 6, 5840–5842.Google Scholar
- Kantz, H., & Schreiber, T. (2004). Nonlinear time series analysis (2nd ed.). Cambridge: Cambridge University Press.Google Scholar
- Lal, A.,Oku, Y., Hülsmann, S., Okada, Y., Miwakeichi, F., Kawai, S., Tamura, Y. & Ishiguro, M. (2010) Dual oscillator model of the respiratory neuronal network generating quantal slowing of respiratory rhythm. Journal of Computational Neuroscience [Epub ahead of print].Google Scholar
- Molkov, Y. I., Abdala, A. P. L., Bacak, B. J., Smith, J. C., Paton, J. F. R., & Rybak, I. A. (2010). Late-expiratory activity: emergence and interactions with the respiratory CPG. Journal of Neurophysiology, doi: 10.1152/jn.00334.2010.
- Pagliardini, S., Tan, W., Janczewski, W. A., & Feldman, J. L. (2009). Excitation and disinhibition of RTN/pFRG neurons induce active expiration in adult rats. In The XI-th Oxford Conference on Modeling and Control of Breathing: New Frontiers in Respiratory Control, Program and Abstracts, Nara, Japan (pp. 101).Google Scholar
- Pikovsky, A., Rosenblum, M., & Kurths, J. (2003). Synchronization: A universal concept in nonlinear sciences (Cambridge Nonlinear Science Series): Cambridge University Press.Google Scholar
- Richter, D. W. (1996). Neural regulation of respiration: Rhythmogenesis and afferent control. In R. Greger & U. Windhorst (Eds.), Comprehensive Human Physiology. From Cellular Mechanisms to Integration, Vol. 2 (pp. 2079–2095). Berlin: Springer-Verlag.Google Scholar
- Rubin, J. E., Hayes, J. A., Mendenhall, J. L., & Del Negro, C. A. (2009a). Calcium-activated nonspecific cation current and synaptic depression promote network-dependent burst oscillations. Proceedings of the National Academy of Sciences of the United States of America, 106, 2939–2944.CrossRefGoogle Scholar
- Rybak, I. A., O'Connor, R., Ross, A., Shevtsova, N. A., Nuding, S. C., Segers, L. S., et al. (2008). Reconfiguration of the pontomedullary respiratory network: a computational modeling study with coordinated in vivo experiments. Journal of Neurophysiology, 100(4), 1770–1799.PubMedCrossRefGoogle Scholar
- Thoby-Brisson, M., Karlen., M, Wu, N., Charnay, P., Champagnat, J., & Fortin G. (2009). Genetic identification of an embryonic parafacial oscillator coupling to the preBötzinger complex. Nature Neuroscience, 12, 1028–U1100.Google Scholar
- Tort, A. B., Kramer, M. A., Thorn, C., Gibson, D. J., Kubota, Y., Graybiel, A. M., et al. (2008). Dynamic cross-frequency couplings of local field potential oscillations in rat striatum and hippocampus during performance of a t-maze task. Proceedings of the National Academy of Sciences of the United States of America, 105(51), 20517–20522.PubMedCrossRefGoogle Scholar