Brain Mechanism Could Be Key to New Stimulants, Anesthetics

By Jon Parham

Researchers in the UAMS Center for Translational Neuroscience discovered that cells in the part of the brainstem that controls sleep, dreaming and waking exhibit the same type of electrical activity as when the cortex of the brain is alert or during learning. This discovery could allow development of new stimulants and anesthetics that can modulate this brain activity, the researchers reported in the May 2010 issue of the Journal of Neurophysiology.

“While we used to believe this system worked like a hammer hitting a bell, causing the cortex to ring, we now find that it is like the hammer itself is also ringing,” said Edgar Garcia-Rill, Ph.D., director of the center and a professor in the Department of Neurobiology and Developmental Sciences of the UAMS College of Medicine.

When awake with our eyes closed, electrodes on the scalp measure waves of brain activity at 10 Hertz, Garcia-Rill said. The activity slows when we sleep.

When a person opens his eyes and is alerted, the activity jumps to 20-40 Hertz, referred to as gamma band activity. The gamma band activity also is present during consciousness, learning and dreaming, Garcia-Rill said, but was believed to have only been present in the cerebral cortex, the thin, convoluted surface of the brain.

UAMS scientists found that parts of the reticular activating system, the part of the brain responsible for regulating arousal and waking, also exhibit gamma band activity. Garcia-Rill noted that the nerve cells in this area prefer to fire at around 40 Hertz, but no higher, when stimulated.
“This means that the reticular activating system activates the rest of the brain when we are alerted, and it does so, not by triggering such activity in other regions, but by itself generating gamma band activity,” he said.

Garcia-Rill said that while the activity of the cells usually increases in frequency, in this case it stays fairly consistent. The next step in the research, he said, will be to explore the membrane channels in the cells to see what could be controlling the cell frequency and keeping it in a stable range.

“Being able to manipulate that frequency holds the key to new stimulants or anesthetics through development of medications that could block or induce that activity – and thus control waking and sleeping more effectively,” Garcia-Rill said.

Christen Simon, a graduate student in the Center for Translational Neurosciences was lead author of the article detailing the discovery, “Gamma band unit activity and population responses in the pedunculopontine nucleus (PPN).” Joining Simon and Garcia-Rill as authors were Nebojsa Kezunovic, graduate student in the Center for Translational Neurosciences, Meijun Ye, Ph.D., a former postdoctoral fellow in the Department of Neurobiology and Development Sciences of the UAMS College of Medicine, James R. Hyde, graduate student in the Center for Translational Neurosciences, Abdallah Hayar, Ph.D., an associate professor in the Department of Neurobiology and Development Sciences of the UAMS College of Medicine, and David K. Williams, Ph.D., an associate professor of biostatistics in the UAMS Fay W. Boozman College of Public Health.

This research was funded by National Institutes of Health grants by the National Institute for Neurological Disorders and Stroke (NS020246) and the National Institute for Research Resources (RR020146).

UAMS is the state’s only comprehensive academic health center, with colleges of Medicine, Nursing, Pharmacy, Health Related Professions and Public Health; a graduate school; a 540,000-square-foot hospital; a statewide network of regional centers; and six institutes: the Winthrop P. Rockefeller Cancer Institute, the Jackson T. Stephens Spine & Neurosciences Institute, the Myeloma Institute for Research and Therapy, the Harvey & Bernice Jones Eye Institute, the Psychiatric Research Institute and the Donald W. Reynolds Institute on Aging. UAMS has 2,775 students and 748 medical residents. It is the state’s largest public employer with more than 10,000 employees, including nearly 1,150 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. Visit or