Integrative Models of Neural Adaptive Control

描述（由申请人提供）：本理论神经科学项目以哺乳动物呼吸控制系统为例，利用现代系统理论综合建模技术来阐明非线性感觉运动系统的自适应控制机制。一个基本的假设是，由传入和传出神经处理的可塑性引起的积分-微分计算和记忆可能会在感觉运动系统的闭环控制中引入非线性动力学。建模与实验相结合的方法包括三个相互关联的步骤。首先，通过比较NMDA受体和5-HT受体依赖的神经可塑性或相关通路损伤前后的反射反应，定量评估神经可塑性对大鼠化学反射和机械反射开环特性的贡献。其次，在类似实验干预前后，评估神经可塑性对呼吸控制系统闭环稳定性和节律性的影响。需要验证的一个主要假设是，短期和长期的神经可塑性对内在的非线性神经动力学有重要贡献，而非线性神经动力学决定了呼吸节律的相对稳定性和相位转换模式。最后，基于这些定量数据，将建立呼吸控制系统的综合模型，以描述在正常和测试条件下观察到的呼吸控制系统的开环和闭环特性。本研究结果将从系统理论的角度从行为层面揭示感觉运动系统的组织和运作原理。特别是，该结果将促进目前对各种异常的呼吸控制机制的理解，包括充血性心力衰竭和高原的睡眠呼吸暂停和呼吸不稳定，以及脑干损伤后的呼吸暂停。

DESCRIPTION (provided by applicant): 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.