Sleep architecture in unrestrained rhesus monkeys (Macaca mulatta) synchronized to 24-hour light-dark cycles.

THE USE OF NONHUMAN PRIMATES AS A MODEL FOR HUMAN SLEEP HAS UNIQUE RELEVANCE TO HUMAN NEUROBIOLOGY. THE CLOSE PHYLOGENETIC relationship and similar diurnal habits of nonhuman primates allow them to fill a gap between sleep studies of rodents or felines and those of humans. The rhesus monkey (Macaca mulatta) was determined to be the best sleep model in a comparison of 13 nonhuman primate species,1 both for its well-defined, human-like sleep organization and for relative ease of husbandry. The rhesus monkey has also been the most extensively used nonhuman primate model for the study of human diseases, including disorders of the nervous system. An extensive knowledge of the physiology of the rhesus monkey also confers an important advantage over the use of other primate species as a model for human sleep. Until recently, studies employing EEG for sleep recordings in rhesus monkeys were necessarily performed using methodological approaches that prevented the expression of normal sleep. For example, potentially confounding manipulations included the need to relocate animals to a novel laboratory setting for recordings, chair restraint and physical tethering of the animals during recording. Although short-term acclimation to the setting was typically (but not always) employed, the animals were nonetheless in an environment unlike their home cages and remained physically restrained for the duration of the sleep recording, forcing the animals to, at a minimum, adopt abnormal sleeping postures. The negative impact of physical restraint on sleep behaviors has been convincingly demonstrated in baboons, which displayed disrupted sleep-wake patterns, unusual drowsiness, and inattentiveness.2 Their sleep patterns also differed from those of animals with externally mounted telemetry that permitted them to move freely in their cages.3 Although no similar comparison of sleep patterns between restrained and unrestrained rhesus monkeys is available, it is known that normal behaviors of rhesus monkeys are markedly affected by chair restraint.4 Restraint induces a number of endocrine changes in rhesus monkeys, including changes in circulating renin, vasopressin, and growth hormone,5 as well as alteration of hemodynamic variables, including cardiac output, blood pressure, and total peripheral resistance.6 Perhaps unsurprisingly then, sleep in restrained rhesus monkeys has shown considerable variability, including marked fragmentation and prolonged bouts of wakefulness during the normal sleep period, suggesting that restraint, novel settings, or other experimental manipulations may have contributed to the inconsistencies seen in prior studies.7–9 Another distinct limitation of most prior rhesus sleep studies has been the relatively short duration of the recording period, which typically consisted of nighttime recordings only, possibly due in part to the limitations of paper polygraph systems. In the present study, sleep recordings of unrestrained rhesus monkeys were made in their home cages using fully implantable biotelemetry transmitters and a computer data collection system, permitting continuous recordings over multiple consecutive days, with battery life lasting up to a year of continuous operation to enable long-term sleep studies. By avoiding novel settings, restraint, backpacks, and other potentially stressful apparatus and manipulations, we anticipated obtaining a more accurate and complete characterization of normal sleep in the rhesus monkey. Specifically, we hypothesized that the rhesus in our study would demonstrate greater sleep consolidation and sleep efficiency (defined by percentage of total time in sleep) during the dark period than previously seen in restrained animals. A better characterization of the undisturbed sleep patterns of rhesus monkeys, particularly where similarities with human sleep could be established, would be an important step in validating the rhesus as a biomedical model of human sleep regulation.