Wakefulness might be
governed by a tiny region
of the brain called the mesopontine
tegmental anesthesia area (MPTA)

Tiny Region of Brain Says 'Lights Out'

September 21, 2009
by Brendon Nafziger, DOTmed News Associate Editor
Researchers in Israel believe anesthesia might act on only a tiny area of the brain, raising hopes of perfecting more targeted anesthetics and shedding light on the mystery of consciousness, according to an article in the Journal of Neuroscience.

"With anesthesia, the presumption is the drug circulates everywhere in the brain," Marshall Devor, Ph.D., a neuroscientist at Hebrew University, tells DOTmed News. Dr. Devor calls this idea the "wet blanket hypothesis," as the drug smothers the "fire" of consciousness by covering the whole brain at once.

But Dr. Devor suspects that the drug doesn't affect the whole brain: just one small "sensor" area.

In the study, Dr. Devor's team found that "a tiny micro-injection -- that is, a very small amount of general anesthetic agent -- on [one] tiny spot in the brain, has basically the same effect as general anesthesia" coursing through the body, he says.

Dr. Devor and his team injected small amounts of the barbiturate pentobarbital into the part of a rat's brain that Dr. Devor calls the mesopontine tegmental anesthesia area, or MPTA, "a very small localized area," he says, found in the reticular formation, a region in the brain stem known to be involved in sleep. Using a thousandth of a dose you would normally use to knock out an animal, Dr. Devor was able to produce an anesthesia-like state in the rat.

"[There was] failure to respond to noxious stimuli," he says, "pain is gone. It loses reflex and muscle tone. Consciousness is lost to the extent we can tell an animal loses consciousness: the EEG [brain waves] goes from a wake pattern to a deep sleep pattern."

Delivering micro-injections of the agent into other parts of the brain had no anesthetic effect on the animals, other than sometimes weakness or tremors in the legs, Dr. Devor says.

Although under the microscope brain cells from the MPTA region don't differ markedly from neighboring ones, Dr. Devor believes they control wakefulness through "wires," or extended connected pathways traveling to higher and lower regions of the nervous system.

"There are projections to certain interesting parts of the brain, and down to the spinal cord -- to possibly turn off pain, and turn off the motor system," Dr. Devor says.

"If pain relief comes from suppressing the entire brain, that's all you can do," says Dr. Devor, but if it comes from only one part of the brain he thinks there are possibilities of creating targeted anesthetics that can control pain without causing loss of consciousness, or even sleeping pills that can better put you to sleep without side effects.

This research might even one day make it possible to help people with otherwise intact brains who are comatose, by stimulating the MPTA region of the brain to wake them up.

But smoother surgeries, sounder sleeps or even helping people in comas are not the only possible implications of the research. "From a science point of view, we're talking about the circuitry of consciousness," Dr. Devor says. If his team really has discovered a "switch" between wakefulness and sleep, it provides new insight into "how the brain manages consciousness," he says. This points to the "deepest and most important and exciting question of neuroscience, or perhaps of science altogether: How does electrical activity and chemical activity become translated into mind?"

Currently, Dr. Devor's lab is investigating neural pathways involved in the MPTA, and also seeing what effect tinkering with them has on alertness. "The fact is we've got a little tiny localized cluster that has widespread control over [other] areas," he says.

"Considering anesthetics have been used for 150 years in surgery -- it's what permits surgery -- it's amazing there are very few labs studying the circuitry involved and how it exactly works," he says.