Experience Sculpts Brain Circuitry to Build
Resiliency to Stress
Rats Develop “Illusion of Control”
It’s long been known that experiencing control over a stressor
immunizes a rat from developing a depression-like syndrome when
it later encounters stressors that it can’t control. Now,
scientists funded by the National Institute of Mental Health (NIMH),
part of the National Institutes of Health (NIH), have unraveled
the workings of the brain circuitry that inoculates against such
hard knocks — the circuitry of resilience.
Control not only activated the brain’s executive hub, the
prefrontal cortex, but also altered it so that it later activated
even when the stressor was not controllable. This activation turned
off mood-regulating cells in the brainstem’s alarm center.
The immunizing effect was so powerful that even a week later, when
confronted with an uncontrollable stressor, the cells behaved as
if the stressor was controllable and the rat was protected.
“It’s as if the original experience with control leads
the animal to later have the illusion of control even when it’s
absent, thereby producing resilience in the face of challenge,” explained
NIMH grantee Steven Maier, Ph.D., University of Colorado. “The
prefrontal cortex is necessary for processing information about
the controllability of stressors as well as applying this information
to regulate responses to subsequent stressors.”
A report on this first study exploring the neural mechanisms by
which an initial experience with a controllable stressor can block
the later behavioral effects of an uncontrollable stressor, by
Maier, Jose Amat, Ph.D., and colleagues, appears in the December
20, 2006 issue of the Journal of Neuroscience.
“Lack of control over stressful life experiences has been
implicated in mood and anxiety disorders,” noted NIMH Director
Thomas Insel, M.D. “Understanding how the brain encodes the
experience of control to protect against such adverse consequences
should help us develop better treatments for these disorders.”
Rats exposed to uncontrollable stress develop a syndrome similar
to depression (http://www.nimh.nih.gov/healthinformation/depressionmenu.cfm)
and post traumatic stresss disorder (PTSD) (http://www.nimh.nih.gov/healthinformation/ptsdmenu.cfm)
in which they lose the ability to learn how to escape stressors
and behave more fearfully.
Maier’s research team had last year reported that the prefrontal
cortex (http://www.nimh.nih.gov/press/ratstress.cfm)
quelled the brainstem center’s alarmist tendencies. The current
study sought to pinpoint how and when the cortex influenced the
alarm center to produce the stress immunity.
The researchers chemically inactivated the cortex at critical
stages of experiencing and reacting to controllable and uncontrollable
stress while measuring neurotransmitter activity and gene expression
in cells of the alarm center via chemical monitoring and brain
mapping techniques. Increased secretion of serotonin (a mood regulating
chemical) and gene expression in the alarm center, as well as the
depression-like behavioral changes, no longer occurred following
an uncontrollable stressor, if a controllable stressor had been
experienced as much as a week earlier.
When the prefrontal cortex was experimentally turned off during
the controllable stressor, the animal failed to develop such immunity.
Similarly, turning the cortex area off prior to the uncontrollable
stress also abolished the usually protective effect of a prior
controllable stress experience. Thus, the prefrontal cortex was
required both at the time of the initial control experience and
then later at the time of challenge for protection to occur.
“Perceived control, or coping, can buffer individuals against
the negative emotional and physiological impact of stress,” said
Maier. “Enhancing the cortex’s control over brainstem
and other stress-responsive structures appears to be critical for
preventing and treating mood and anxiety disorders.”
Also participating in the study were Evan Paul, Christina Zarza,
and Linda Watkins, Ph.D., University of Colorado.
The National Institute of Mental Health (NIMH) mission is
to reduce the burden of mental and behavioral disorders through
research on mind, brain, and behavior. More information is available
at the NIMH website (www.nimh.nih.gov).
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov. |