The mechanism by which we regain
consciousness following general anesthetic has so far been poorly
understood. In a paper published in the journal PNAS, the researchers
demonstrate that activating dopamine neurons in the ventral tegmental
area (VTA) of the brain causes active emergence from general anesthesia.
The use of general anesthesia for surgery has not changed
fundamentally since it was first introduced 170 years ago. Patients are
still left to come around in their own time following withdrawal of the
However, some patients can take a considerable amount of time to
wake up, holding up the use of expensive operating rooms and occupying
medical staff who must keep them under close observation.
‘Activating dopamine neurons in the ventral tegmental area (VTA) of the brain causes active emergence from general anesthesia.’
Now researchers at MIT and Massachusetts General Hospital have moved
a step closer to a treatment to rapidly awaken patients after
administration of a general anesthetic, following a study of the
mechanism that allows people to regain consciousness.
Ken Solt, a research affiliate in the
Department of Brain and Cognitive Sciences at MIT and an
anesthesiologist at Massachusetts General Hospital, led the research
alongside Emery Brown, the Edward Hood Taplin Professor of Medical
Engineering and Computational Neuroscience at MIT and an
anesthesiologist at Massachusetts General Hospital.
"The process of how the neural circuits come back online following
anesthesia has not really been studied in depth, and this is something
that interested us from a clinical standpoint, because we are
investigating ways to rapidly reverse anesthesia," Solt says.
The researchers have previously demonstrated that Ritalin, the drug
commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD),
can bring anesthetized rats out of anesthesia almost immediately.
Ritalin is a stimulant that increases levels of the neurotransmitter
dopamine, which is known to promote wakefulness. But the specific
dopamine circuits in the brain that regulate arousal from an anesthetic
To determine the precise mechanism involved, the researchers used
optogenetics to selectively activate dopamine neurons in the VTA of
The researchers first engineered dopamine neurons in the mice's VTA
to express light-sensitive proteins. They were then able to activate
these specific neurons by shining blue laser light at them.
The engineered mice were placed under a steady dose of anesthetic
until they were unconscious and on their backs. Lying on their back in
this way is a sure sign that a rodent is unconscious, as even while
asleep their righting reflex would normally cause them to flip onto
their front sides to make them less vulnerable to predators.
The researchers then activated the neurons with light, causing them
to release dopamine. This prompted the animals to immediately wake up
and flip over, and in many cases to begin walking around.
"Dopamine neurons in the VTA are traditionally thought of as playing
a key role in reward, motivation, and drug addiction but had not really
been well characterized in the context of arousal," Solt says. "But we
discovered that by activating dopamine neurons in this very specific
part of the brain, we were able to reverse the state of general
anesthesia and wake up the animals."
As well as freeing up valuable operating room time, developing a
treatment to rapidly bring people out of anesthesia may also lessen the
side effects, according to Brown.
For example, many people feel groggy after anesthesia and find that their brains do not work very well.
"We want to get the patient's cognitive processes back to exactly
where they were before they had anesthesia," Brown says. "It's a given
that a high fraction of older patient's brains in particular will not
work as well after anesthesia."
The researchers have also found that Ritalin can improve respiratory
function, which can also be adversely affected by anesthesia.
The researchers are now conducting further experiments in mice to
determine whether cognitive function is fully restored following
anesthesia when using Ritalin.
They are also carrying out trials of Ritalin in humans, to confirm that it does accelerate recovery from general anesthetic.
"We have all seen that perfect wake-up following general anesthesia,
where the patient is talking and perfectly comfortable and out of the
recovery room in a very short period of time," says Brown, who is also
the associate director of MIT's Institute for Medical Engineering and
Science. "Every anesthetic should end in this way, but it will never
happen if anesthesiologists stay wedded to their old processes," he
"We are trying to create a new phase for anesthesia practice in
which you actively turn someone's brain back on after having general