Sleep need Wakefulness

The importance of adenosine deaminase in the duration and intensity of sleep in humans has been noted recently (Retey et al. 2005). Animal studies suggest that sleep needs are genetically controlled, and this also seems to apply in humans. Probably, a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and slow wave activity during sleep. Thus low activity of the catabolic enzyme for adenosine results in elevated adenosine, and deep sleep. In contrast, insomnia patients could have a distinct polymorphism of more active adenosine deaminase resulting in less adenosine accumulation, insomnia, and a low threshold for anxiety. This could also explain interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers. This could affect the EEG during sleep and wakefulness in a non-state-specific manner. 

Mathematical analyses of EEG SWA have yielded quantitative information about the time course of accumulation and discharge of sleep need. The dynamics of the sleep/wake-dependent changes in delta power have been quantified with the use of computer simulations, and delta power can now be predicted in detail. The increase of sleep need during waking can be described by an exponentially saturating curve with a time constant (Tj) of 18.2 hr in humans (37) and 8.6 hr in... 

The compensations for lost sleep suggest that the master control of total sleep may not reside in specific, localizable sleep effectors or neuromodulators, but in a stimulus generated by the need for sleep. Presumably, this need-stimulus activates several sleep centers and substances and deactivates wake centers and substances, which then contribute to the production of sleep to the extent that they are affected. (Conceivably, a need for wakefulness might conversely activate wake mechanisms and deactivate sleep mechanisms.) If one sleep or wake effector were destroyed or blocked by experimental or natural intervention, the need-generated stimulus would opportunistically recruit whatever systems were available to answer the need. When the need was satisfied, the effector systems would remain inactive no matter how prepared they were to function. 

Accordingly, insofar as the sleep or wake need was not grossly perturbed by biological or environmental upheaval, sleep and wake amounts would remain stable even though the mix of effector contributions might vary in response to other factors. 

With this in mind, the search for molecular markers that define populations of neurons in areas important for arousal is clearly warranted. In this chapter we describe the identification of four peptidergic systems that modulate different aspects of the sleep-wakefulness cycle. The success of this strategy demonstrates the need for new markers of neuronal cell types, which may define populations of neurons critical for our understanding of cortical activity and sleep. 

Many animals hibernate during parts of the year, entering a state that is similar to a very deep sleep. But hibernation is more than simply a deep sleep. The animal s body temperature drops well below its normal range, the animal does not wake up for a long period of time, and its metabolism slows to the point that the animal does not need to eat or relieve itself during that period. 

The net result is that in one brain-activated state, waking, the brain is in touch with the outside world and can act upon it, whereas in another equally activated state, REM sleep, it cannot do either. In both cases, the activation is real and important and must constitute a dimension of any model. But so diametrically opposed are the input-output conditions of waking and REM that they cannot possibly be dealt with by an activation-only model. We need the input-output (TO) dimension. 

One of the most instructive examples of state boundary crossing is the tendency to experience dreamlike visuomotor sensations at sleep onset. These are called hypnagogic hallucinations if the subject is still awake enough to notice or be aroused by them. Apparently, one need only carry waking brain activation over the sleep boundary and dreaming will im-... 

The narcolepsy story is important not only because it explains the sleep disorder itself, but because we can use it to begin to understand the normal dynamics of brain state transitions. The narcolepsy story supports the general hypothesis that state margins are fuzzy, not sharp ragged, not smooth and mushy, not crisp. State transitions need finite amounts of time to be fully accomplished. Because so many subsystems of the brain participate it is not surprising that one (or two) should lag behind (or lead) the rest. The net result is that we can be in two states at once waking and dreaming. 

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