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. ? ?
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