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

Hebrew University discovery opens door to future treatment of impaired-consciousness disorders.

By JUDY SIEGEL-ITZKOVICH
brain 88 (photo credit: )
brain 88
(photo credit: )
A tiny cluster of nerve cells in the upper brain stem has been identified by Hebrew University of Jerusalem researchers for the first time as being an essential part of the "circuit" that controls states of unconsciousness. The groundbreaking work, based on years of working on rats and likely to be applicable to humans, could lead to future treatments for loss of consciousness, sleep disorders and pain. It was recently published as a 12-page article in the Journal of Neuroscience. Prof. Marshall Devor, the Cecile and Seymour Alpert professor of pain research - who worked with graduate student Ruth Abulafia and research associate Dr. Vladimir Zalkind - told The Jerusalem Post on Monday that this small group of cells appeared to have "executive control" over many brain functions, but not over involuntary ones like blood pressure or respiration. He speculated that this specific part of the brain - called MPTA, or the mesopontine tegmental anesthesia area - could have been what was turned off by G-forces, lack of oxygen or blood glucose, or other factors when fighter pilot Capt. Assaf Ramon suddenly lost consciousness in his plane as it made a sharp turn, and crashed on Sunday. The discovery of a specific cluster of neurons that control the brain's state of consciousness is expected to lead to better understanding of the actual wiring diagram that permits the brain to be conscious. Although much more research is needed, Devor said that eventually, greater understanding of the MPTA and its connections could lead to the reversal of some types of coma, treatment of insomnia or excessive sleepiness, as well as pain relief. "Maybe some forms of coma not due to widespread brain damage are related to damage of neurons only in the MPTA," he suggested. "It is very speculative, but if it's true that losing consciousness results from suppression of cells in the MPTA, maybe some patients could be awakened from their comas with direct electrical stimulation of this cluster 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 vitamin capsule," Devor said. "Our discovery is very different from the classical idea of brain starvation." Brain scientists have conventionally believed that consciousness is lost all at once, like pulling out the electrical plug of a computer from its power source. They presume that this constellation of dramatic functional changes reflects widely distributed suppression of neuronal activity in the brain due to dispersed drug action or to widespread oxygen or nutrient starvation. This situation puts the person in an anesthesia-like state, so he or she does not feel pain or remember, the brain metabolism declines, and the muscles are flaccid. Loss of response to painful stimuli and loss of consciousness are the most striking characteristics of surgical anesthesia and anesthesia-like states such as a concussion, reversible coma and syncope (fainting). But Devor and his team suggest a radically different architecture - that this relatively small number of neurons near the base of the brain work together to have executive control over the alert status of the entire cerebrum and spinal cord through specific brain circuitry and can trigger the loss of pain sensation, postural collapse 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" in laboratory rats, rather than giving them anesthesia in the conventional way by injection into a vein, which they did in a control group of rats. Injections to the MPTA immediately induced a profound suppressive effect on the activity of their cerebral cortexes. Studies on the rats found that the nerve pathway that involves pain (a pathway the researchers were able to follow) connects the MPTA with the spinal cord, while the pathway involved in alertness - which affects sleep - links the MPTA to the cortex of the brain. The circuit that makes muscles flaccid goes down the spinal cord, while that involved in memory reaches the memory sensor in the brain, Devor explained. "I know of only a handful of labs in the world that have worked on brain circuitry related to anesthesia," he said, adding that a possible next step would be to do clinical studies, examining human brains harmlessly using functional MRI scans to view the MPTA area while a person undergoes anesthesia. "In the meantime, we want to continue working on rats, which are larger than mice and easier to work with," said Devor, who has been conducting a whole series of studies on rat brains for around nine years. "Maybe a drug could be designed that would activate a specific receptor and provide pain control without the other effects of anesthesia, such as loss of consciousness, while another could cause arousal without muscle weakness," he concluded.