Nakao M, McGinty D, Szymusiak R, Yamamoto M
Neurophysiology and Bioinformatics Laboratory, Graduate School of Information Sciences, Tohoku University, Sendai, Japan.
J Biol Rhythms. 1999 Dec;14(6):547-56. doi: 10.1177/074873099129000885.
Thermoregulatory mechanisms were hypothesized to provide primary control of non-rapid-eye-movement sleep (NREM). On the basis of this hypothesis, we incorporated the thermoregulatory feedback loops mediated by the "heat memory," heat load, and loss processes associated with sleep-wake cycles, which were modulated by two circadian oscillators. In addition, hypnogenic warm-sensitive neurons (HWSNs) were assumed to integrate thermoregulation and NREM control. The heat memory described above could be mediated by some sleep-promoting substances. In this paper, considering the possible carrier of the heat memory, its losing process is newly included in the model. The newly developed model can generate the appropriate features of human sleep-wake patterns. One of the special features of the model is to generate the bimodal distribution of the sleepiness. This bimodality becomes distinct, as the losing rate of the heat memory decreases or the amplitude of the Y oscillator increases. The theoretical analysis shows the losing rate of the heat memory control's rapidity of model response to a thermal perturbation, which is confirmed by simulating the responses with various losing rates to transient heat loads ("heat load pulse"). The sleepiness exhibits large responses to the heat load pulses applied in the early and late phases of wake period, while the response is significantly reduced to the pulse applied in the supposed wake-maintenance zone. This bimodality of the response appears to reflect the sensitivity of the HWSNs. In addition, the early pulse raises the immediate sleepiness rather than the nocturnal sleepiness, while the heat load pulse applied in the later phase of waking period significantly raises the sleepiness during a nocturnal sleep. In simulations of sleep deprivation, the discontinuous relationship between recovery sleep length and deprivation time is reproduced, where the critical sleep deprivation time at which the recovery sleep length jumps is extended as the losing rate increases. This is possibly due to the dissipation of the heat memory accumulated by the sleep deprivation. The simulation results here qualitatively reproduce the experimental observations or predict the intriguing phenomena of human circadian rhythms. Therefore, our model could provide a novel framework for investigating the relationship between thermoregulation and sleep control processes.
体温调节机制被假定为对非快速眼动睡眠（NREM）起主要控制作用。基于这一假设，我们纳入了由“热记忆”介导的体温调节反馈回路、热负荷以及与睡眠 - 觉醒周期相关的散热过程，这些过程由两个昼夜节律振荡器调节。此外，假定催眠性温敏神经元（HWSNs）整合体温调节和NREM控制。上述热记忆可能由一些促进睡眠的物质介导。在本文中，考虑到热记忆可能的载体，其丢失过程被新纳入模型。新开发的模型能够生成人类睡眠 - 觉醒模式的适当特征。该模型的一个特殊特征是产生困倦的双峰分布。随着热记忆的丢失率降低或Y振荡器的振幅增加，这种双峰性变得更加明显。理论分析表明热记忆的丢失率控制着模型对热扰动响应的速度，这通过模拟对瞬态热负荷（“热负荷脉冲”）具有不同丢失率的响应得到了证实。困倦对在觉醒期早期和晚期施加的热负荷脉冲表现出较大反应，而对在假定的觉醒维持阶段施加的脉冲反应则显著降低。这种反应的双峰性似乎反映了HWSNs的敏感性。此外，早期脉冲提高的是即时困倦而非夜间困倦，而在觉醒后期施加的热负荷脉冲则显著提高夜间睡眠期间的困倦程度。在睡眠剥夺模拟中，再现了恢复睡眠时间与剥夺时间之间的不连续关系，即恢复睡眠时间跳跃的临界睡眠剥夺时间随着丢失率的增加而延长。这可能是由于睡眠剥夺积累的热记忆的消散。这里的模拟结果定性地再现了实验观察结果或预测了人类昼夜节律的有趣现象。因此，我们的模型可以为研究体温调节与睡眠控制过程之间的关系提供一个新的框架。
