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.
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
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
"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
"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.
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