Thermoregulatory model of sleep control: losing the heat memory.

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.