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RESEARCH HIGHLIGHT Nearly all of us have had a traumatic experience
at some point in our lives, but most of us
can move on and go about our daily business. People with post-traumatic stress disorder
(PTSD), however, experience recurrent
fear and anxiety that never seems to go
away, even long after the traumatic event
is over. An MBRS-supported researcher in
Puerto Rico was part of a team that identified
one area of the brain that may be
essential for learning how not to be afraid.
The researchers suggest that people with
PTSD may have impaired function in the
front part of the brain, called the prefrontal
cortex. MBRS researcher Dr. Gregory Quirk
and graduate student Mohammed Milad
at the Ponce School of Medicine have
studied this area of the brain by recording
electrical activity in the prefrontal cortex
of laboratory rats. The team conditioned
the rats to fear a sound the scientists
played while delivering a foot shock to
the rats. They measured fear by the degree
to which the rats became immobilized,
known as the freezing response. Repeated
presentations of the sound without the
shock caused fear responses to slowly
disappear, a process researchers call
extinction of the response. Classic behavioral experiments
dating back to Pavlov’s dogs have
suggested that extinction does not
erase a fear association
from memory, but
instead generates a new safety memory to
block the fear response. According to this
theory, some part of the brain must create
the safety memory by increasing its activity
after extinction. In the November 7,
2002, issue of the journal Nature, Milad
and Quirk showed for the first time that
nerve cells in the prefrontal cortex
increased their activity in response to the
sound only after extinction, creating what
the researchers called a “safety signal.”
The team found that the more active this
brain region was, the less afraid the rats
were when they heard the sound. The rats
with the most prefrontal cortex
activity acted as if they had never been
conditioned to fear at all. The scientists’
findings lend support to the idea that
fear reduction is an active process. Milad and Quirk, who both receive
funding from the National Institute of
Mental Health, did more experiments
with the rats and learned that stimulating
one particular region of the prefrontal
cortex diminished the rats’ fear response.
When the researchers electrically stimulated the prefrontal cortex in rats that had
never exhibited extinction and paired the
stimulation with the sound, the stimulated
rats displayed little fear, acting as if their
fear response had been erased. Later, these
rats continued to be unafraid of the sound
even without stimulation. What could be going on? The researchers speculate that since
the prefrontal cortex sends signals to the
amygdala, which is a cluster of nerve cells
in the brain that stores memories, including
those of fear, stimulating the
prefrontal cortex may directly impact
the ability to remember a fear response.
The findings also suggest the exciting
possibility that stimulating the prefrontal
cortex could someday be used to strengthen
the extinction response in people with
anxiety disorders. Reference: Milad MR, Quirk GJ. Neurons
in medial prefrontal cortex signal memory
for fear extinction. Nature 2002;420:70-4. Research Highlights features the research
being done by current and former students
and faculty in the MARC, MBRS, and
other NIGMS minority programs. We
welcome your story ideas and suggestions
for future Research Highlights items. |
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