LeDoux Lab 2010 SfN Abstracts

Program#/Poster#:	914.20/MMM36
Title:	Extinction and synapse specific disruption of Pavlovian fear memories without emotional expression
Location:	Halls B-H
Presentation Time:	Wednesday, Nov 17, 2010, 4:00 PM - 5:00 PM
Authors:	*K. K. COWANSAGE1, L. DIAZ-MATAIX2, M.-H. MONFILS4, J. E. LEDOUX3,5; 1Ctr. Neural Sci., New York Univ., NEW YORK, NY; 2Ctr. for Neural Sci., 3New York Univ., New York, NY; 4The Univ. of Texas at Austin, Austin, NY; 5The Emotional Brain Inst. and the Nathan Kline Inst., Orangeburg, NY
Abstract:	The ability to attend to meaningful stimuli in the environment, while disregarding irrelevant noise, depends on core brain mechanisms for contrast detection and adaptation. Through complex signal processing systems, a discrete sensory event, delineated in time and space by a rapid onset and offset switch, can be distinguished from a persistent background context. Under some conditions, a neutral conditioned stimulus (CS) can acquire particular emotional relevance through its association with a meaningful unconditioned stimulus (US), like painful footshock. In such cases, the discrete moment of CS onset is frequently observed to serve as a trigger for CS-elicited behavior (i.e. fear-induced freezing), which typically persists for the duration of the CS presentation. Seminal work by Kamin (1963) has shown that the level of contrast between a CS and its preceding background can modulate the efficacy of Pavlovian learning. However, it is unclear how the perceptual and physiological switch that coincides with CS onset regulates memory reactivation and corresponding behavior. To address this question, rats were strongly trained (20s 5kHz tone + 0.8mA footshock, x3) and 24hrs later, received a test of long-term memory (LTM) consisting of a 270-sec test chamber acclimation followed by two CS presentations. The next day, these rats were again re-tested with the same CS, introduced at the time of box entry, and thus without a pre-CS acclimation period. We found that when a fear-eliciting CS was presented immediately upon box entry, as a ramping perceptual experience rather than as a discrete on-off switch, freezing behavior was completely suppressed, and rats explored the chamber freely for the entire CS presentation, regardless of its duration. Intriguingly, while this “no-switch” onset condition failed to elicit fear expression, it did not prevent either extinction or post-reactivation disruption of the memory by propranolol. Since most current methods of fear reduction, including extinction and blockade of reconsolidation, require initial fear expression in order to activate and manipulate memory, the current results provide a novel approach by which to access a specific memory trace without triggering the associated fear experience.
Support:	R01 MH46516 R37 MH38774 K05 MH067048 P50 MH58911