Neurobiology of REM and NREM sleep☆
Introduction
This paper presents an overview of the current knowledge of the neurophysiology and cellular pharmacology of sleep mechanisms. It is written from the perspective that recent years have seen a remarkable development of knowledge about sleep mechanisms, due to the capability of current cellular neurophysiological, pharmacological and molecular techniques to provide focused, detailed, and replicable studies that have enriched and informed the knowledge of sleep phenomenology and pathology derived from electroencephalographic (EEG) analysis. This chapter has a cellular and neurophysiological/ neuropharmacological focus, with an emphasis on rapid eye movement (REM) sleep mechanisms and non-REM (NREM) sleep phenomena attributable to adenosine. A detailed historical introduction to the topics of this chapter is available in the Steriade and McCarley book [1]. For the reader interested in an update on the terminology and techniques of cellular physiology, one of the standard neurobiology texts can be consulted (e.g., [2]). Overviews of REM sleep physiology are also available [1], [3], as well as an overview of adenosine and NREM sleep [4]. The present paper draws on these accounts for the text, and we begin with brief and elementary overviews of sleep architecture and phylogeny/ontogeny to provide a basis for the later mechanistic discussions. Part I treats REM sleep and the relevant anatomy and physiology, and then comments very briefly on the role of hypocretin/orexin in REM sleep control. Part II discusses NREM sleep in the context of adenosinergic mechanisms.
Sleep may be divided into two phases. REM sleep is most often associated with vivid dreaming and a high level of brain activity. The other phase of sleep, NREM sleep or slow wave sleep (SWS), is usually associated with reduced neuronal activity; thought content during this state in humans is, unlike dreams, usually nonvisual and consists of ruminative thoughts. As one goes to sleep, the low voltage fast EEG of waking gradually gives way to a slowing of frequency and, as sleep moves toward the deepest stages, there is an abundance of delta waves, EEG waves with a frequency of 0.5 to <4 Hz and of high amplitude. The first REM period usually occurs about 70 min after the onset of sleep. REM sleep in humans is defined by the presence of low voltage fast EEG activity, suppression of muscle tone (usually measured in the chin muscles) and the presence, of course, of rapid eye movements. The first REM sleep episode in humans is short. After the first REM sleep episode, the sleep cycle repeats itself with the appearance of NREM sleep, and then about 90 min after the start of the first REM period, another REM sleep episode occurs. This rhythmic cycling persists throughout the night. The REM sleep cycle length is 90 min in humans and the duration of each REM sleep episode after the first is approximately 30 min. While EEG staging of REM sleep in humans usually shows a fairly abrupt transition from NREM to REM sleep, recording of neuronal activity in animals presents quite a different picture. Neuronal activity begins to change long before the EEG signs of REM sleep are present. To introduce this concept, Fig. 1 shows a schematic of the time course of neuronal activity relative to EEG definitions of REM sleep. Later portions of this chapter will elaborate on the activity depicted in this figure. Over the course of the night, delta wave activity tends to diminish and NREM sleep has waves of higher frequencies and lower amplitude.
Section snippets
REM sleep
REM sleep is present in all mammals, and recent data suggest that this includes the egg-laying mammals (monotremes), such as the echidna (spiny anteater) and the duckbill platypus. Birds have very brief bouts of REM sleep. REM sleep cycles vary in duration according to the size of the animal, with elephants having the longest cycle and smaller animals having shorter cycles. For example, the cat has a sleep cycle of approximately 22 min, while the rat cycle is about 12 min. In utero, mammals spend
NREM sleep and adenosine
This section focuses on nonrapid eye movement (NREM) sleep and adenosine, with a special focus on the basal forebrain. Another chapter in this volume discusses hypothalamic sleep mechanisms.
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This work was supported by grants from the Department of Veterans Affairs, Medical Research Service and NIMH (R37 MH39,683 and R01 MH40,799).