This theoretical neuroscience project uses modern systems-theoretic integrative modeling techniques to elucidate the mechanisms of adaptive control of nonlinear sensorimotor systems, as exemplified by the mammalian respiratory control system. A fundamental assumption is that the integral-differential computation and memory resulting from the plasticity of afferent and efferent neural processing may introduce nonlinear dynamics in the closed-loop control of sensorimotor systems. The combined modeling-experimental approach will involve three interlocking steps. First, the contributions of neural plasticity to the open-loop characteristics of chemoreflex and mechanoreflex in rats will be assessed quantitatively by comparing these reflex responses before and after pharmacological suppression of NMDA receptor- and 5-HT receptor dependent neural plasticity or lesioning of related pathways. Second, the effects of neural plasticity on the closed-loop stability and rhythmicity of the respiraotry control system will be assessed before and after similar experimental interventions. A major hypothesis to be tested is that short-term and long-term neural plasticity contribute importantly to the intrinsic nonlinear neurodynamics that determines the relative stability and phase-switching patterns of the respiratory rhythm. Finally, based on these quantitative data an integrative model of the respiratory control system will be formulated in order to describe the observed openloop and closed-loop characteristics of the respiratory control system in normal and test conditions. The outcome of this research will shed light on the organizing and operating principles of sensorimotor systems at the behavioral level from a systems-theoretic perspective. In particular, the results will advance the current understanding of the mechanism of respiratory control in a variety of abnormalities including sleep apnea and respiratory instability in congestive heart failure and high altitude, and apneustic breathing after brainstem damage. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072849-02
Application #
6913599
Study Section
Special Emphasis Panel (ZRG1-IFCN-E (03))
Program Officer
Twery, Michael
Project Start
2004-07-01
Project End
2008-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
2
Fiscal Year
2005
Total Cost
$400,000
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Song, Gang; Wang, Hui; Xu, Hui et al. (2012) Kölliker–Fuse neurons send collateral projections to multiple hypoxia-activated and nonactivated structures in rat brainstem and spinal cord. Brain Struct Funct 217:835-58
Straus, Christian; Samara, Ziyad; Fiamma, Marie-Noelle et al. (2011) Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta. Am J Physiol Regul Integr Comp Physiol 300:R1163-74
Song, G; Xu, H; Wang, H et al. (2011) Hypoxia-excited neurons in NTS send axonal projections to Kölliker-Fuse/parabrachial complex in dorsolateral pons. Neuroscience 175:145-53
Song, Gang; Tin, Chung; Poon, Chi-Sang (2010) Bilateral lesions of pontine Kölliker-Fuse nuclei provoke apnea instead of apneusis in anesthetized adult rats. Adv Exp Med Biol 669:185-8
Poon, Chi-Sang (2010) Homeostatic competition: evidence of a serotonin-gated spinoparabrachial pathway for respiratory and thermoregulatory interaction. Adv Exp Med Biol 669:61-5
Tin, Chung; Wasserman, Karlman; Cherniack, Neil S et al. (2010) Paradoxical potentiation of exercise hyperpnea in congestive heart failure contradicts Sherrington chemoreflex model and supports a respiratory optimization model. Adv Exp Med Biol 669:69-72
Samara, Ziyad; Raux, Mathieu; Fiamma, Marie-Noëlle et al. (2009) Effects of inspiratory loading on the chaotic dynamics of ventilatory flow in humans. Respir Physiol Neurobiol 165:82-9
Lee, Chuang-Chung J; Anton, Mihai; Poon, Chi-Sang et al. (2009) A kinetic model unifying presynaptic short-term facilitation and depression. J Comput Neurosci 26:459-73
Bantikyan, Armenak; Song, Gang; Feinberg-Zadek, Paula et al. (2009) Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity. Pflugers Arch 457:1147-59
Song, Gang; Poon, Chi-Sang (2009) Lateral parabrachial nucleus mediates shortening of expiration and increase of inspiratory drive during hypercapnia. Respir Physiol Neurobiol 165:9-12

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