DESCRIPTION (provided by applicant): There is no consensus as to the function(s) of sleep. This is the central issue underlying both clinical and basic science investigations of sleep. One assumption that has become ascendant in recent years is that all animals sleep for the same reason, albeit a reason that has not yet been discovered. This leads to the reasonable conclusion that investigations of sleep and sleep function should be focused on the simplest animals. A search of the CRISP database for the words "Drosophila" and "sleep" lists 38 NIH programs. However, I am not aware of any current NIH supported work on sleep in mammals other than the already well understood "standard lab mammals," mostly rodents, cats and primates. Similar genetic mechanisms undoubtedly underlie some aspects of the control of sleep- like states in mammals and invertebrates and are being revealed by studies of Drosophila, zebrafish and C. elegans. However, our recent work and analysis of the literature presents evidence for a great diversity of sleep behavior, physiology and neurochemistry. Major differences exist even between mammalian species in terms of the presence and regulation of REM and nonREM sleep, sleep rebound and sleep EEG. This diversity is particularly obvious when comparing marine and land mammals. Of particular interest is sleep in the fur seal and other otariids. These animals have bilateral sleep that is indistinguishable from that seen in the dog and other studied mammals when they are on land, but when the are in water they have unihemispheric nonREM sleep and little or no REM sleep for very long periods of time. This startling deviation from the normal mammalian sleep pattern does not produce any ill effects or any sleep rebound when the fur seal returns to land. Investigation of unihemispheric sleep in these mammals will allow us to, for the first time, clearly distinguish neuronal mechanisms linked to the sleep state from those linked to behavioral quiescence with its associated heart rate, muscle tone, respiration and body temperature reductions. They will allow us to identify core anatomical, neurochemical and neurophysiological elements of sleep common to the cat, rat, human and fur seal, and any neurological control mechanisms unique to the fur seal. In pursuance of these objectives, we will use bilateral in vivo microdialysis to monitor the release of key neurotransmitters during these states, Fos immunohistochemistry to identify cell groups active during unihemispheric sleep, bihemispheric sleep and waking, and brainstem and forebrain temperature measurement to identify thermoregulatory changes correlated with these states. A full understanding of the evolution, regulation and function of sleep in humans can only be achieved by understanding the diversity and commonalities of mammalian sleep. PUBLIC HEALTH RELEVANCE: When fur seals are in water, their home for 6 months of the year, they have sleep in only one half of the brain and body at a time, greatly reduce or eliminate REM sleep and frequently forgo sleep entirely for periods of several days, a sleep pattern that resembles that of whales and dolphins. Understanding how and why this very unusual sleep pattern occurs will provide fundamental insights into the functions of REM and nonREM sleep, the key mysteries in sleep research. It will also allow us to determine the location and specific roles of each of the neuronal groups active during sleep. This would have implications for the understanding of diseases characterized by REM sleep abnormalities in humans, including narcolepsy, depression and REM sleep behavior disorder. It would also provide an insight into the causes of insomnia.

7. Project Narrative When fur seals are in water, their home for 6 months of the year, they have sleep in only one half of the brain and body at a time, greatly reduce or eliminate REM sleep and frequently forgo sleep entirely for periods of several days, a sleep pattern that resembles that of whales and dolphins. Understanding how and why this very unusual sleep pattern occurs will provide fundamental insights into the functions of REM and nonREM sleep, the key mysteries in sleep research. It will also allow us to determine the location and specific roles of each of the neuronal groups active during sleep. This would have implications for the understanding of diseases characterized by REM sleep abnormalities in humans, including narcolepsy, depression and REM sleep behavior disorder. It would also provide an insight into the causes of insomnia.