Neural modeling for cooperative/competitive regulation of REM sleep with NREM sleep and wakefulness

Recently, we proposed the model consists of a quartet of neuron groups: (1) sleep-active preoptic/anterior hypothalamic neurons (N-R group); (2) wake-active hypothalamic and brain-stem neurons exhibiting the highest rate of discharge during wakefulness and the lowest rate of discharge during paradoxical or REM sleep (WA group); (3) brain-stem neurons exhibiting the highest rate of discharge during REM sleep (REM group); and (4) basal forebrain, hypothalamic, and brain-stem neurons exhibiting a higher rate of discharge during both wakefulness and REM sleep than during NREM sleep (W-R group). In this chapter, we explain our revised model of sleep–wakefulness regulation in the rat, which includes a neural regulator quartet of NREM sleep, REM sleep, wakefulness, and a coregulator of REM sleep and wakefulness, whose parameters are tuned up so that the model reproduces some of the recent findings concerning the WA neurons. The physiological reality of the model structure is demonstrated by comparing the model neuron activities with the actual neuronal activities across state transition. Among the conceptual and mathematical models, one of the novel features of our model is involvement of the cholinergic W-R neuron group, which is assumed to contribute toward induction of wakefulness as well as REM sleep by selectively mediating autocatalytic activation with the WA or REM neurons. Through activity of this neuron group, the wakefulness–sleep flip-flop and the REM–NREM flip-flop interact with each other in our model. In fact pharmacological or physiological manipulations of REM sleep were shown to affect not only NREM sleep but wakefulness. Our successful modeling suggests that REM sleep is regulated cooperatively/competitively with NREM sleep and wakefulness by well orchestrated interactions among the aforementioned quartet of neural groups distributed in the hypothalamus and the brain stem with the aid of sleep-promoting substances. Finally, further possible updates in the model structure are described considering recent physiological findings.