| Program#/Poster#: |
591.19/UU6 |
| Title: |
Lateral amygdala infusions of corticotropin-releasing
factor have opposing effects on formation and expression of fear conditioning
|
| Location: |
Washington Convention Center: Hall A-C
|
| Presentation Time: |
Tuesday, Nov 18, 2008, 10:00 AM -11:00
AM |
| Authors: |
K. ISOGAWA, *D. E. BUSH, J. E.
LEDOUX;
Ctr. Neural Sci., New York Univ., New York, NY |
| Abstract: |
The amygdala is known to be a primary
component of the neural circuitry underlying Pavlovian fear conditioning,
an emotional learning paradigm that involves forming an association between
an initially neutral conditioned stimulus (CS; e.g. a tone) and an innately
aversive unconditioned stimulus (US; usually footshock). The lateral nucleus
of the amygdala (LA) is an initial site of convergence for CS and US information
in the brain. Corticotropin-releasing-factor (CRF) is a neuropeptide implicated
in the control of both behavioral and endocrine responses to stress, and
the LA contains high levels of CRF-1 receptors. However, the role of LA
CRF receptors in fear conditioning is not well understood. Here we assessed
the effects of CRF infusions into the LA and central amygdala (CE) on both
the acquisition and expression of fear conditioning. First we injected CRF
(0, 3, 30 or 300 ng/0.25µl/side) into LA 1 hour before auditory fear conditioning
(1 tone-footshock pairing). Two days later, rats were tested for CS-elicited
freezing in a distinct context. Rats given pre-training CRF showed a dose-dependent
suppression of freezing. In the next experiment we injected CRF (0 or 30
ng/0.25µl/side) into LA 1 hour before the fear memory test. Rats given
pre-testing CRF showed a facilitation of freezing. Finally, in order to
determine whether or not the effects were attributable to CRF diffusion
into CE, where CRF cell bodies and receptors are present, we repeated the
pre-training and pre-testing experiments with CE infusions. Results showed
that CRF infusions into CE had no effect at either time point. Thus, CRF
infusions into LA disrupted the formation, but enhanced the expression,
of fear conditioning. These findings may have important implications for
understanding mechanisms underlying contributions of stress to fear-related
disorders. In major depressive disorder (MDD) patients and posttraumatic
stress disorder (PTSD) patients, CRF in cerebrospinal fluid is higher than
control subjects. These patients readily retrieve past aversive emotional
memories but form new aversive emotional memories with difficulty. CRF effects
in LA may contribute to the development of MDD and PTSD symptoms. |
| Support: |
R37 MH038774, P50 MH058911, R01 MH046516,
K05 MH067048 |