Simulating Microinjection Experiments in a Novel Model of the Rat Sleep-Wake Regulatory Network
Simulating Microinjection Experiments in a Novel Model of the Rat Sleep-Wake Regulatory Network
复制标题
DOI：
10.1152/jn.00795.2009
复制
发表时间：
2010-04-01
影响因子：
2.5
通讯作者：
Booth, Victoria
中科院分区：
文献类型：
--
作者：
Behn, Cecilia G. Diniz;Booth, Victoria
在大鼠睡眠-觉醒调节网络的新模型中模拟显微注射实验。中国生物医学工程学报（自然科学版）39(3):357 - 357,2010。首次发表于2010年1月27日；doi: 10.1152 / jn.00795.2009。本研究提出了一种新颖的数学模型框架，特别适合于研究脑干和下丘脑的睡眠-觉醒调节网络的结构和动力学。它是基于一个群体放电率模型的形式，修改明确包括神经递质释放到突触后群体的浓度水平。利用这一框架，模拟了参与大鼠睡眠觉醒调节的初级脑干和下丘脑神经元核之间的相互作用。该模型网络捕获了真实的大鼠多相睡眠-觉醒行为，包括清醒、快速眼动（REM）睡眠和非快速眼动（NREM）睡眠状态。网络动力学包括非快速眼动睡眠、快速眼动睡眠和清醒状态的循环模式，该模式被神经递质释放的模拟变异性和网络的外部噪声所破坏。明确的神经递质浓度模型允许模拟神经递质激动剂和拮抗剂微注射到关键的唤醒促进群体，蓝斑（LC）。这些模拟显微注射对睡眠-觉醒状态的影响被跟踪并与实验观察结果进行比较。激动剂/拮抗剂对被认为对LC活性有相反的影响，但通常不会对睡眠-觉醒模式产生相反的影响，因为网络中LC激活的机制多种多样。此外，不同的药物，被认为对LC活性有平行影响，但由于激动剂和拮抗剂作用的状态依赖性或独立性的差异，不会对睡眠-觉醒模式产生平行影响。这些模拟结果强调了形式化数学建模对约束睡眠-觉醒调节网络概念模型的实用性。
Diniz Behn CG, Booth V. Simulating microinjection experiments in a novel model of the rat sleep-wake regulatory network. J Neurophysiol 103: 1937-1953, 2010. First published January 27, 2010; doi: 10.1152/jn.00795.2009. This study presents a novel mathematical modeling framework that is uniquely suited to investigating the structure and dynamics of the sleep-wake regulatory network in the brain stem and hypothalamus. It is based on a population firing rate model formalism that is modified to explicitly include concentration levels of neurotransmitters released to postsynaptic populations. Using this framework, interactions among primary brain stem and hypothalamic neuronal nuclei involved in rat sleep-wake regulation are modeled. The model network captures realistic rat polyphasic sleep-wake behavior consisting of wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep states. Network dynamics include a cyclic pattern of NREM sleep, REM sleep, and wake states that is disrupted by simulated variability of neurotransmitter release and external noise to the network. Explicit modeling of neurotransmitter concentrations allows for simulations of microinjections of neurotransmitter agonists and antagonists into a key wake-promoting population, the locus coeruleus (LC). Effects of these simulated microinjections on sleep-wake states are tracked and compared with experimental observations. Agonist/antagonist pairs, which are presumed to have opposing effects on LC activity, do not generally induce opposing effects on sleep-wake patterning because of multiple mechanisms for LC activation in the network. Also, different agents, which are presumed to have parallel effects on LC activity, do not induce parallel effects on sleep-wake patterning because of differences in the state dependence or independence of agonist and antagonist action. These simulation results highlight the utility of formal mathematical modeling for constraining conceptual models of the sleep-wake regulatory network.