J'lem researchers find brain's 'center of alertness'

A tiny cluster of nerve cells in the upper brainstem has been identified by Hebrew University of Jerusalem researchersfor the first time as being an essential part of the "circuit" thatcontrols states of unconsciousness.

Thegroundbreaking work, based on years of working on rats and likely to beapplicable to humans, could lead to future treatments for loss ofconsciousness, sleep disorders and pain. It was recently published as a12-page article in the Journal of Neuroscience.

Prof. Marshall Devor, the Cecile and Seymour Alpert professor ofpain research - who worked with graduate student Ruth Abulafia andresearch associate Dr. Vladimir Zalkind - told The Jerusalem Poston Monday that this small group of cells appeared to have "executivecontrol" over many brain functions, but not over involuntary ones likeblood pressure or respiration.

He speculated that this specific part of the brain - calledMPTA, or the mesopontine tegmental anesthesia area - could have beenwhat was turned off by G-forces, lack of oxygen or blood glucose, orother factors when fighter pilot Capt. Assaf Ramon suddenly lostconsciousness in his plane as it made a sharp turn, and crashed onSunday.

The discovery of a specific cluster of neurons thatcontrol the brain's state of consciousness is expected to lead tobetter understanding of the actual wiring diagram that permits thebrain to be conscious. Although much more research is needed, Devorsaid that eventually, greater understanding of the MPTA and itsconnections could lead to the reversal of some types of coma, treatmentof insomnia or excessive sleepiness, as well as pain relief.

"Maybe some forms of coma not due to widespread brain damageare related to damage of neurons only in the MPTA," he suggested. "Itis very speculative, but if it's true that losing consciousness resultsfrom suppression of cells in the MPTA, maybe some patients could beawakened from their comas with direct electrical stimulation of thiscluster of cells."

In rats, the MTPA is about 3 mm. long, 1 mm. across and 1 mm. deep, like a cylinder.

"In humans, it would of course be much bigger, maybe 1.5 cm.long, and 3 or 4 cm. in width and depth, about the shape of a vitamincapsule," Devor said. "Our discovery is very different from theclassical idea of brain starvation."

Brain scientists have conventionally believed thatconsciousness is lost all at once, like pulling out the electrical plugof a computer from its power source. They presume that thisconstellation of dramatic functional changes reflects widelydistributed suppression of neuronal activity in the brain due todispersed drug action or to widespread oxygen or nutrient starvation.

This situation puts the person in an anesthesia-like state, sohe or she does not feel pain or remember, the brain metabolismdeclines, and the muscles are flaccid. Loss of response to painfulstimuli and loss of consciousness are the most striking characteristicsof surgical anesthesia and anesthesia-like states such as a concussion,reversible coma and syncope (fainting).

But Devor and his team suggest a radically differentarchitecture - that this relatively small number of neurons near thebase of the brain work together to have executive control over thealert status of the entire cerebrum and spinal cord through specificbrain circuitry and can trigger the loss of pain sensation, posturalcollapse and loss of consciousness through specific neural circuitry.

The team injected tiny amounts of pentobarbital, an anesthetic,directly into the newly discovered "center of consciousness" inlaboratory rats, rather than giving them anesthesia in the conventionalway by injection into a vein, which they did in a control group ofrats. Injections to the MPTA immediately induced a profound suppressiveeffect on the activity of their cerebral cortexes.

Studies on the rats found that the nerve pathway that involvespain (a pathway the researchers were able to follow) connects the MPTAwith the spinal cord, while the pathway involved in alertness - whichaffects sleep - links the MPTA to the cortex of the brain. The circuitthat makes muscles flaccid goes down the spinal cord, while thatinvolved in memory reaches the memory sensor in the brain, Devorexplained.

"I know of only a handful of labs in the world that have workedon brain circuitry related to anesthesia," he said, adding that apossible next step would be to do clinical studies, examining humanbrains harmlessly using functional MRI scans to view the MPTA areawhile a person undergoes anesthesia.

"In the meantime, we want to continue working on rats, whichare larger than mice and easier to work with," said Devor, who has beenconducting a whole series of studies on rat brains for around nineyears.

"Maybe a drug could be designed that would activate a specificreceptor and provide pain control without the other effects ofanesthesia, such as loss of consciousness, while another could causearousal without muscle weakness," he concluded.