LOS ANGELES, April 4, 2007 (PRIME NEWSWIRE) -- Clifford B. Saper, M.D., Ph.D., known as one of the world's foremost neuroanatomists for creating "neural maps" of the brain's complex circuitry that have led to advances in treating obesity, Parkinson's Disease, Alzheimer's Disease and schizophrenia, was featured in The Saban Distinguished Lecturer Series at the Saban Research Institute of Childrens Hospital Los Angeles on Tuesday, April 3, 2007. Dr. Saper discussed "Hypothalamic Regulation of Sleep and Circadian Rhythms."
Dr. Saper is the James Jackson Putnam Professor of Neurology and Neuroscience at Harvard Medical School, and chairman of the Harvard department of Neurology at Beth Israel Deaconess Medical Center in Boston.
"Clif Saper is a major force in neuroendocrine neuroscience and has made numerous discoveries impacting a variety of clinical areas including cardiovascular regulation, obesity and sleep research," said Richard Simerly, Ph.D., director of the Neuroscience Program at The Saban Research Institute and a professor of Pediatrics, Keck School of Medicine of the University of Southern California. "One of the things that characterizes Dr. Saper's work is his ability to combine first-rate neuroanatomical observations with careful measurements of functional activity."
"Dr. Saper's work has contributed significantly to our appreciation of how the brain regulates essential bodily functions at the level of complex functional neural systems," Dr. Simerly said, adding that work in his own lab is focused on how the hormone leptin influences development of neural pathways regulating body weight. "Much of what we know about leptin signaling in these pathways came out of Dr. Saper's laboratory."
Introducing Dr. Saper to the Saban Research Institute audience, Dr. Simerly recalled that as a graduate student, he had spent days poring over scientific papers written by Dr. Saper and his team.
"Together with Dr. Larry Swanson of USC, who was in the same laboratory at the time, Clif Saper published some of the most significant papers on the hypothalamus," said Dr. Simerly. "It was clear these people were working at a very different level than most...his attention to anatomical detail and physiological context is really what characterizes the work that he does: the highest level of neuroanatomical sophistication, combined with a deep understanding of physiology, as he explores the functional significance of the complex brain circuitries that regulate how the hypothalamus controls the autonomic nervous system, and some of the basic things that keep us alive, like sleeping and eating."
Dr. Saper graduated from the University of Illinois, with both bachelor's and master's degrees in biology, and then as an M.D./Ph.D. student at Washington University in St. Louis, he studied neuroscience in the laboratory of Dr. Maxwell Cowan.
Following a residency in neurology at Cornell University Medical Center in New York, Dr. Saper returned to St. Louis and joined the neurobiology faculty at Washington University. He moved to the University of Chicago in 1985, where he became the William D. Mabie Professor of Neurology and Neuroscience. In 1992, he became a member of the faculty at Harvard University and chair of the Department of Neurology at its Beth Israel Deaconess Medical Center, and he was named editor-in-chief of the Journal of Comparative Neurology, the leading journal for neuroanatomical research.
During his lecture before the Saban Research Institute audience, Dr. Saper explained that the brain has a series of cell groups in the brainstem (the lowest part of the brain) that activate the forebrain (the parts involved in thinking), and keep them awake.
"The process of sleep is an active one," he explained, "and it requires the shutting down of those activating networks."
"The way this is done," he said, "is by a 'master switch' in the hypothalamus (a very old part of the brain, just above the pituitary gland, behind the eyes). This switch is the ventrolateral preoptic (VLPO) nucleus, and it can turn off all of the arousal circuits at once, thus allowing sleep to occur. When this switch is damaged, it causes inability to sleep, which can be quite severe."
The discovery of the "sleep switch" in the brain that turns off arousal systems so that sleep may occur has helped redefine scientists' understanding of how the brain regulates sleep.
"As we age," Dr. Saper said, "the neurons in the nucleus of the VLPO steadily deteriorate. We think this explains why older people have trouble sleeping, and why they wake up early. We think it's due to damage in the nerve cells in the brain."
During his lecture, Dr. Saper also discussed how the brain's biological clock organizes cycles of sleep and wakefulness. "The brain's main clock is in the suprachiasmatic nucleus or SCN," he explained. "The SCN receives signals about the day-night cycle from the visual system, and passes that information on to another cell group, the dorsomedial nucleus (DMH) that then organizes the wake-sleep cycles, as well as cycles of activity, feeding and hormones such as cortisol.
"However, when animals only have access to food during the normal sleep cycle, they can adapt to that, and switch all their activity cycles over so as to be awake and alert when the food is available. In animals that are placed in this situation, like the Norwegian brown bat, the DMH develops its own clock, which overrides the SCN, and establishes a new cycle to make sure that the animal has the best chance for survival."
In the 1970s, Dr. Saper identified the feedback loop between internal organs and the brain that translates emotions into physical responses.
The current focus of the Saper laboratory at Harvard is on the integrated functions maintained by the hypothalamus. These include regulation of wake-sleep cycles, body temperature and feeding. "Basic regulation of sleep, body temperature and feeding - although they seem quite separate, they interact with one another in very profound ways," he explained. "All three are driven by homeostatic mechanisms, as well as by circadian influences. In addition, all three must be adjusted in response to external stressors, ranging from immune stimuli, to food or sleep deprivation, to behavioral stress."
In addition to studying neural circuit function in experimental animals, the Saper laboratory also is interested in identifying homologous circuitry in human brains, and in determining how it may be disrupted in specific neurological and psychiatric disorders. Together with the basic research on animal models, this translational approach is providing new clues about the origins of a variety of neurological disorders including Alzheimer's Disease, Tourette Syndrome, schizophrenia and Prader-Willi Syndrome.
Founded in 1901, Childrens Hospital Los Angeles has been treating the most seriously ill and injured children in Los Angeles for more than a century, and it is acknowledged throughout the United States and around the world for its leadership in pediatric and adolescent health. Childrens Hospital is one of America's premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California for more than 75 years. It is a national leader in pediatric research.
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