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Research
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Garcia-Rill lab
garciarilledgar@uams.edu
 Work in Dr. Garcia-Rill's lab is directed at the development of rapid eye
movement (REM) sleep, which decreases drastically from birth (50% of sleep time)
until after puberty (15% of sleep time). The hypothesis being tested is that a dysregulation of REM sleep during development will lead to lifelong increases in
REM sleep drive and hypervigilance, as is evident in schizophrenia, anxiety
disorders and depression.
Recent findings suggest that inputs to the pedunculopontine nucleus (PPN),
which is the cholinergic arm of the reticular activating system (RAS), and
appears to control waking and REM sleep, change dramatically during the
developmental decrease in REM sleep.
PPN neurons showed gradually decreasing depolarization to NMDA, and
increasing depolarization to kainic acid, application in slices from day 12-21
rats. The developmental decrease in REM sleep in the rat occurs from 10-30 days.
These findings suggest that REM sleep may be preferentially controlled by
kainate receptors, while NMDA receptors may be controlling waking. This line of
research suggests that kainite receptor blockers may be useful in the treatment
of disorders that manifest increased REM sleep drive.
Kobayashi, T., Good, C., Biedermann, J., Barnes, C., Skinner, R.D. and
Garcia-Rill, E. Developmental changes in pedunculopontine (PPN) neurons. J.
Neurophysiol. 91: 1470-1481, 2004.
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UAMS
News Bureau,
Office of Communications & Marketing,
4301 West Markham # 890,
Little Rock, AR 72205-7199, www.uams.edu/newsbureau/
News Release, July
19, 2007
Media Contacts:
Leslie W. Taylor, 501-686-8998, Wireless phone: 501-951-7260,
leslie@uams.edu,
Andrea Peel, 501-686-8996, Wireless phone: 501-351-7903,
andrea@uams.edu
LITTLE ROCK - How do we wake up? How do we shift from
restful sleep to dreaming? Researchers at the University of Arkansas for Medical
Sciences (UAMS) have discovered a new brain mechanism that just might explain
how we do that. This new mechanism also may help us understand how certain
anesthetics put us to sleep and how certain stimulants wake us up.
In their first published study on this topic, researchers in the
UAMS Center for Translational Neuroscience found that some neurons in the
reticular activating system, a region of the brain that controls sleep-wake
states, are electrically coupled.
"By finding methods for increasing the electrical coupling of these
cells, we create a stronger pathway for potential sleep-wake control," said
study author Edgar Garcia-Rill, Ph.D., a professor of
neurobiology and developmental sciences in the UAMS College of Medicine and
director of the Center for Translational Neuroscience.
"The possible applications range from the ability to wake people up
from anesthesia or put them to sleep more rapidly, to stimulating someone in a
comatose state to awaken if there are enough of these cells left alive to join
together," Garcia-Rill said.
The study, "Evidence for Electrical Coupling in the
SubCoeruleus (SubC) Nucleus," documenting this cellular new mechanism, was
published in the April issue of the Journal of Neurophysiology (http://jn.physiology.org/).
In June, the research team presented additional findings at the annual meeting
of the Associated for Professional Sleep Societies in Minneapolis.
The researchers found that neurons in the SubCoeruleus nucleus, a
part of the brain believed to control the phase of deep sleep known as
rapid-eye-movement (REM) sleep, joined in a way that allowed them to transmit
electrical activity across the cells. The activity occurred spontaneously or
could be induced by chemical agents that induce REM sleep.
The research article was accompanied by an editorial that called
the finding "seminal" in the field of sleep-wake research. The editorial was
written by peers Matthew Ennis of the Department of Anatomy and Neurobiology at
the University of Tennessee Health Center in Memphis and Subimal Datta of the
Department of Psychiatry and Behavioral Neuroscience at the Boston University
School of Medicine.
"The findings of [the researchers] provide novel and exciting
avenues for understanding sleep-wake control as well as for the treatment of
sleep and arousal disorders," wrote Ennis and Datta in the editorial.
Lead author of the study was David S. Heister, a graduate student
pursuing a combined medical and doctoral degree in the Department of
Neurobiology and Developmental Sciences of the UAMS Graduate School and UAMS
College of Medicine.
Joining Heister and Garcia-Rill are Abdallah Hayar, Ph.D., and
Amanda Charlesworth, Ph.D., UAMS faculty members in the Department of
Neurobiology and Developmental Sciences and researchers in the Center for
Translational Neuroscience; Charlotte Yates, Ph.D., from the Department of
Physical Therapy at the University of Central Arkansas; and former UAMS faculty
member Yi-Hong Zhou, Ph.D., of the University of California-Irvine.
The researchers pointed to earlier work with animal models showing
that stimulation of a specific region of the brain, the reticular activating
system, produced electrical activity similar to that seen during waking and REM
sleep. In studying the SubCoeruleus section of the brain, the researchers
detected the presence of electrical coupling of cells similar to the kind that
showed an ability to switch between the REM and waking state. The presence of
electrical coupling between these cells offers a potential pathway for
substances that could regulate the sleep-wake control, Garcia-Rill said.
The electroencephalogram, or EEG, of the waking brain shows
fast rhythms of 10-50 cycles per second, while the sleeping brain cycles at
frequencies below 10 per second. Electrical coupling would allow many cells to
fire together, generating a rhythm that is transmitted to other parts of the
brain to induce changes in sleep-wake states. In collaboration with the chemical
transmitters that control the firing rates in individual cells, the two
mechanisms could generate any of the frequencies seen in the EEG. Some
anesthetics are known to block gap junctions, the channels by which electrical
coupling takes place, while some stimulants increase electrical coupling.
Garcia-Rill helped establish the UAMS Center for
Translational Neuroscience in 2003 as a division of the Department of
Neurobiology and Developmental Sciences supported by a Center of Biomedical
Research Excellence award from the national Center for Research Resources at the
National Institutes of Health. It is one of the
few facilities in the nation devoted to quickly moving new treatments from basic
scientific research to developing new treatments for patients in the clinic. The
CTN is part of the Jackson T. Stephens Spine & Neuroscience Institute. The
Center for Translational Neuroscience also has a Community Research and
Education Core Facility that works to bring clinical treatments to the medical
and lay community.
UAMS is the state's only comprehensive academic health center, with
five colleges, a graduate school, a medical center, six centers of excellence
and a statewide network of regional centers. UAMS has 2,435
students and 714 medical residents. It is one
of the state's largest public employers with about 9,400 employees, including nearly 1,000
physicians who provide medical care to patients at UAMS, Arkansas Children's
Hospital, the VA Medical Center and UAMS' Area Health Education Centers
throughout the state. UAMS and its affiliates have an
economic impact in Arkansas of $5
billion a year. For more information, visit
www.uams.edu.
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