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History of Sleep Research By Dr. Ron Harper

UCLA has pioneered a substantial number of findings that established the basis for our current knowledge of sleep and sleep disorders, and continues to have the largest group of basic and clinical sleep researchers in the U.S. An early founder of the medical school and first chair of the Department of Anatomy, Dr. Horace Magoun, had been instrumental in outlining the brain mechanisms of sleep and waking with his studies of the reticular formation, a concept that provided the basis for understanding how the brain maintained arousal and induced sleep for over 50 years. An early recruit to Magoun's Department, Dr. Carmine Clemente, with his student, Barry Sterman, and native-Poland colleague, Dr. Wanda Wywricka, described the brain areas underlying the "quiet" state of sleep, findings which now are being rediscovered with newer technology. The early years of sleep research were marked by visitors and students who went on to become world-renowned in the field, and include Michel Jouvet from Lyons, who contributed much to the understanding of rapid eye movement (REM) sleep. During this period, remarkable findings in the endocrine and sleep field were being outlined by Dr. Charles (Tom) Sawyer. Training of young researchers has been a major focus over the years, and was supported by NIH-funded training programs and workshops at the UCLA Arrowhead retreat. Residency training programs, such as that of Dr. Santiago in the West LA Veterans Administration have also assisted.

Dr. Ron Harper

At the same time these early basic studies were being conducted, Dr. Anthony Kales was describing patterns of sleep and waking in humans, and laying the basis for pharmacologic studies in sleep. Dr. Kales, together with a major figure in sleep research from the University of Chicago, Dr. Rechtschaffen, chaired a group which established the first atlas for scoring human sleep in 1967. That atlas formed the basis for scoring of normal and abnormal sleep until the first revision in 2007. After Dr. Kales moved to Pennsylvania, a human sleep laboratory was continued in the Department of Psychiatry and Biobehavioral Sciences, with Dr. Emory Zimmermann as director; he was superceded by Dr. Frisca Yan-Go, and the laboratory was moved to the Department of Neurology.

A finding that outlines the principal mechanism underlying obstructive sleep apnea was described by Drs.' Ronald Harper and Ebohardt Sauerland with the first description of upper airway muscle (tongue muscle) activity during sleep. Those studies pointed to the natural narrowing of the airway that accompanies the paralysis of those muscles during REM sleep, and formed the basis for understanding obstructive sleep apnea. At the same time, Dr. Michael Chase was outlining the brain mechanisms responsible for that muscle paralysis, and evaluating how those changes developed in early life. Drs.' Dennis McGinty and Ronald Harper also described the properties of a brain system, the serotonergic system, during sleep. Serotonin plays a significant role in arousal, in temperature regulation and in depression and mood, as well as sleep.

Sleep researchers at UCLA (Drs. Sterman, Harper, McGinty) joined with researchers at Women's Hospital, USC to follow the development of infant sleep to determine the mechanisms which cause Sudden Infant Death Syndrome (SIDS), a collaborative study with USC Women's hospital (Drs.' Hodgman and Hoppenbrouwers). This study was the largest project of its kind, and clarified many of the potential mechanisms by which SIDS could result in a fatal outcome during sleep.

Significant studies on the mechanisms underlying narcolepsy, a debilitating disorder with inordinate need to sleep at inappropriate times have been performed with Dr. Jerome Siegel at the Veterans Administration Hospital at North Hills. Dr. Siegel also described the action of brain structures and neurotransmitters involved in the muscle paralysis of sleep, and continues to study interactions of sleep brain mechanisms and other neurological motor disorders. He has also focused on the underlying mechanisms for the need for sleep, examining those processes through sleep patterns in different species. Drs.' Ron Syzmusiak and Dennis McGinty have outlined the role of neurons in the basal forebrain which contribute to temperature regulation and which begin and maintain sleep, and Dr. Christopher Colwell has examined basic mechanisms regulating 24 hour rhythms over function. Many of Dr. Colwell's studies examine the interaction of neurotransmitters with circadian pacing structures, an especially important relationship in determining influences of circadian effects on mood-affected and other syndromes. The current UCLA Chancellor, Dr. Gene Block, also has a distinguished history in circadian research.

Current research at UCLA focuses heavily on determining the brain structures which fail to support breathing during sleep in children, cause disordered breathing during sleep in adults, or are injured as a consequence of sleep disordered breathing or failure in regulation of glucose in diabetic patients. Dr. E. Pae studies basic mechanisms in the nature of hypoxic injury in obstructed breathing. Drs. Ron Harper, Mary Woo, Paul Macey, Frisca Yan-Go and Rajesh Kumar have found, through magnetic resonance imaging studies, that sleep disordered breathing, such as obstructive sleep apnea, causes severe brain alterations, and results in changes in brain structure which are associated with depression and other mood disorders. This team also found severe alterations in the brain of heart failure patients, a condition which is associated with severely impaired nocturnal breathing. Dr. Michael Irwin heads a program to evaluate the interaction of immunology and sleep, an area increasingly recognized as essential to the understanding of disease conditions affected by altered immune states; sleep and immune action are closely integrated, with many of the deleterious effects of sleep disorders potentially mediated by immune responses.

The major focus of current studies is to determine how major debilitating syndromes, including diabetes, depression, heart failure in adults, and Sudden Infant Death Syndrome and sleep disordered breathing in children are influenced by brain mechanisms during sleep. The UCLA investigators use a range of procedures, ranging from magnetic resonance imaging to basic studies of neurotransmitter action to evaluate these interactions.