LeDoux Lab 2008 SfN Abstracts
 
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