Technical advances have often precipitated quantum leaps in the understanding of neurobiological processes. For example, Hans Berger's discovery in 1929 that electrical potentials recorded from the human scalp took the form of sinusoidal waves, the frequency of which was directly related to the level of wakefulness of the subject, led to rapid advances in the understanding of sleep-wake regulation, in both animals and humans alike.¹ To this day the electroencephlogram (EEG), in conjunction with the electromyogram (EMG), i.e., electrical activity produced by skeletal muscles, represents the data "backbone" of nearly every experimental and clinical assessment that seeks to correlate behavior and physiology with the activity of cortical neurons in behaving animals, including humans. In most basic sleep research laboratories these EEG recordings are performed by using a cable-based system (Figure 1) wherein acquired data is subjected off-line to pattern and spectrum analysis [e.g., applying a fast Fourier transform (FFT) algorithm] to determine the vigilance state of the subject being recorded.^{2, 3} Sleep consists of rapid-eye movement (REM) and non-REM (NREM) sleep. REM sleep is characterized by a rapid low-voltage EEG, random eye movement, and muscle atonia, a state in which the muscles are effectively paralyzed. REM sleep is also known as paradoxical sleep, because the brain activity resembles that of wakefulness, whereas the body is largely disconnected from the brain and appears to be in deep sleep. By contrast, motor neurons are stimulated during NREM sleep but there is no eye movement. Human NREM sleep can be divided into 4 stages, whereby stage 4 is called deep sleep or slow-wave sleep and is identified by large, slow brain waves with delta activity between 0.5 – 4 Hz in the EEG. On the other hand, a subdivision between phases of NREM sleep in smaller animals, like rats and mice, has not been established, mostly because they do not have long consolidated periods of sleep as seen in humans.

Over the years, and on the basis of EEG interpretation, several models of sleep-wake regulation, both circuit- and humoral-based, have been proposed. The neural and cellular basis of the need for sleep or, alternatively, "sleep drive," remains unresolved, but has been conceptualized as a homeostatic pressure that builds during the waking period and is dissipated by sleep. One theory is that endogenous somnogenic factors accumulate during wakefulness and that their gradual accumulation is the underpinning of sleep homeostatic pressure. While the first formal hypothesis that sleep is regulated by humoral factors has been credited to Rosenbaum's work published in 1892⁴, it was Ishimori^{5, 6} and Pieron⁷ who independently, and over 100 years ago, demonstrated the existence of sleep-promoting chemicals. Both researchers proposed, and indeed proved, that hypnogenic substances or 'hypnotoxins' were present in the cerebral spinal fluid (CSF) of sleep-deprived dogs.⁸ Over the past century several additional putative hypnogenic substances implicated in the sleep homeostatic process have been identified (for review, see ref. 9), including prostaglandin (PG) D_2,¹⁰ cytokines,¹¹ adenosine,¹² anandamide,¹³ and the urotensin II peptide.¹⁴

Experimental work by Economo^{15, 16}, Moruzzi and Magoun¹⁷, and others in the early and mid-20^th century produced findings that inspired circuit-based theories of sleep and wakefulness and, to a certain degree, overshadowed the then prevailing humoral theory of sleep. To date, several "circuit models" have been proposed, each informed by data of varying quality and quantity (for review, see ref. 18). One model, for example, proposes that slow-wave sleep is generated through adenosine-mediated inhibition of acetylcholine release from cholinergic neurons in the basal forebrain, an area mainly consisiting of the nucleus of the horizontal limb of the diagonal band of Broca and the substantia inominata.¹⁹ Another popular model of sleep/wake regulation describes a flip-flop switch mechanism on the basis of mutually inhibitory interactions between sleep-inducing neurons in the ventrolateral preoptic area and wake-inducing neurons in the hypothalamus and brain stem.^{18, 20, 21} Moreover, for the switching in and out of REM sleep, a similar reciprocally inhibitory interaction has been proposed for areas in the brain stem, that is the ventral periaqueductal gray, lateral pontine tegmentum, and sublaterodorsal nucleus.²² Collectively, these models have proven valuable heuristics and afforded important interpretative frameworks for studies in sleep research; however, a yet fuller understanding of the molecular mechanisms and circuits regulating the sleep-wake cycle will require a more complete knowledge of its components. The system for polygraphic recording detailed below should aid in this goal.