Revving up the Brain Revving up the Brain
National Center for Research Resources

When a person sleeps, the brain hums slowly, like an idling automobile engine. The slower the engine idles, the deeper the sleep. As the engine is revved up, a person wakes up and—provided the foot remains on the accelerator—stays awake. Researchers at the NCRR-funded Center for Translational Neuroscience in Little Rock, Ark., have now discovered how that process works.

During sleep, two parts of the brain, called the thalamus and cortex, take turns firing at rhythms below 10 oscillations per second. For a person to wake up, oscillations between the thalamus and cortex need to speed up to around 40 per second. In the past, researchers believed that sleep and waking were controlled by chemicals called neurotransmitters. But these chemicals, although crucial to brain functioning, might not create rhythms that are sufficiently fast to keep the brain awake and alert.

The new research, published in the April 2007 issue of the Journal of Neurophysiology and in the November 2007 issue of the journal Sleep, shows that groups of nerve cells in a region of the brain stem called the reticular activating system (RAS) communicate electrically through tiny openings in their membranes, or gap junctions. Cells that communicate this way are said to be coupled. “An electrical message moves across a whole population of coupled cells extremely quickly, synchronizing their firing,” says lead author Edgar Garcia-Rill, director of the Center for Translational Neuroscience. “Think of this process like the clapping of hands by an audience. If the clapping is synchronized, the sound is louder.”

Groups of cells in the reticular activating system (RAS) of the brain communicate electrically with one another through tiny openings in their membranes. Such cells are said to be electrically coupled. The photo shows two RAS cells injected with fluorescent dye filling the cell body and dendrites visualized using a confocal microscope. Photo courtesy of Edgar Garcia-Rill, Center for Translational Neuroscience.
When the RAS in the brain receives a signal from the outside world, such as a loud noise, it fires, essentially stepping on the accelerator. The firing causes oscillations between the thalamus and cortex of the brain to speed up. These faster oscillations, called gamma rhythm, alert higher centers of the brain and cause a person to wake up. Gamma rhythms occur during both waking and rapid eye movement sleep, the time when we dream. “People remember dreams and waking hours because the brain is revved up,” explains Garcia-Rill.

The work sheds new light into the nature of wakefulness and sleep, but it also has important medical implications. “If you know that waking up people has to do at least partially with gap junctions, the same mechanism could explain why some anesthetics put you to sleep,” explains Garcia-Rill. “Armed with this knowledge, you could explore treating coma patients with drugs that modulate gap junctions.”

Indeed, researchers at New York University recently discovered that the stimulant modafinil, a drug approved for people with the sleep disorder narcolepsy, could increase the “coupling” of cells through gap junctions (Urbano et al. Proc. Natl. Acad. Sci. U.S.A. 104:12554–12559, 2007).

In addition, because the sleep-wake cycle is thought to be disturbed in certain psychiatric disorders, the knowledge gained through Garcia-Rill’s research might eventually be used to develop new treatments for anxiety disorders, depression, and schizophrenia.