Sleep and wakefulness

There have been many references in this book to the role of neurotransmitters in the control of CNS excitability. It is therefore appropriate, but possibly foolhardy, to see if the two natural extremes of that excitability, namely sleep and waking, can be explained in terms of neurotransmitter activity. Of course, these states are not constant our sleep can be deep or light and, even when we are awake, our attention and vigilance fluctuate, as the reading of these pages will no doubt demonstrate. Also, the fact that we sleep does not mean that our neurotransmitters are inactive this would imply that sleep is a totally passive state, whereas all the evidence suggests that it is an actively induced process, subject to refined physiological control. 

It is most probable that sleep and waking stem from an inherent cycle of neuronal activity that can be influenced dramatically by changes in sensory stimulation. This is demonstrable not only in humans and laboratory animals, but also in invertebrates. Thus, while we cannot be sure that other animals sleep in the same way that we do, they do show a circadian cycle of motor activity. In some (nocturnal) species, such as the rat, this activity is actually highest during darkness. Even aplysia, the sea hare, has such a rhythm but this is more like that of humans in being maximally active during daylight (diurnal). 

The precise role of melatonin in sleep and waking is uncertain but it seems to act as a go-between for the light and biological cycles and evidence suggests that it has a reciprocal relationship with the SCN (Fig. 22.3). Its actions are mediated by (MLi) receptors which are found predominantly in the SCN as well as thalamic nuclei and the anterior pituitary. These are G protein-coupled receptors, with seven transmembrane domains, that inhibit adenylyl cyclase. Their activation by melatonin, or an MLi agonist such as 2-iodomelatonin, restores the impaired circadian cycle in aged rats. 

Figure 22.4 Idealised EEG-like patterns in sleep and waking. When we are awake and aroused the EEG is desynchronised (a). As we become drowsy and pass into sleep the EEG waves become more synchronised with 8-12 Hz alpha waves (b), sleep spindles then appear (c) before the EEG becomes even more synchronised with slow (about 1-2 Hz) high-voltage waves characteristic of deep slow-wave sleep (SWS). About every 90 min this pattern is disrupted and the EEG becomes more like that in arousal (d) except that the subject remains asleep. This phase of sleep is also characterised by rolling, rapid eye movements, the so-called REM sleep. SWS is consequently also known as non-REM sleep. These tracings have been drawn to show the main features of the different EEG phases of sleep and as such are much simpler than those that are actually recorded...

The more synchronised the activity of the cortical neurons, the greater the summation of currents and the larger and slower the EEG wave, as in the sleep pattern (Fig. 22.4). While there are some dissociations between EEG pattern and behavioural states, the EEG offers one way of determining experimentally the pathways (and neurotransmitters) that control arousal and sleep, and can be regarded as an important objective measurement of the cortical correlates of sleep and waking. 

This neurotransmitter presents something of a paradox in respect of its role in sleep and waking behaviour, although its importance to both is undoubted. Early experiments... 

Figure 22.9 Summary of the influence of varying factors on sleep and waking. The EEG is shown diagramatically in the typical arousal (awake) state and in both non-REM (slow wave) and REM sleep. Appropriate activity levels, high or low, are shown for the different factors such as light input, melatonin secretion or ACh, NA, and 5-HT function in the different phases...

Bjorvatn, B and Ursin, R (1998) Changes in sleep and wakefulness following 5-HTlA ligands given systemically and locally in different brain regions. Rev. Neurosci. 9 265-273. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

Neurochemistry of Sleep and Wakefulness, ed. J. M. Monti et al. Published by Cambridge University Press. Cambridge University Press 2008. 

Alam, Md. N., Szymusiak, R., Gong, H., King, J McGinty, D. (1999). Adenosinergic modulation of rat basal forebrain neurons during sleep and waking neuronal recording with microdialysis. J. Physiol. (Lond.) 521(3), 679-90. 

Saper, C. B., Chou, T. C., Scammel, T. E. (2001). The sleep switch hypothalamic control of sleep and wakefulness. Trends Neurosci. 24, 726-31. 

John, J., Wu, M. F., Boehmer, L. N. Siegel, J. M. (2004). Cataplexy-active neurons in the hypothalamus implications for the role of histamine in sleep and waking behavior. Neuron 42, 619-4. 

Monti, J. M. Jantos, H. (1992). Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat. J. Sleep Res. 1,... 

Morales, F. R. Chase, M. H. (1978). Intracellular recording of lumbar motoneuron membrane potential during sleep and wakefulness. Exp. Neurol. 62, 821-7. 

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