*K. K. COWANSAGE, M.-H. MONFILS, J. E. LEDOUX;
Ctr. Neural Sci., New York Univ., New York, NY

In the conventional Pavlovian auditory fear conditioning paradigm, rats manifest a behavioral fear response to an inherently neutral conditioned stimulus (CS), often a tone, when it predictably coincides with an aversive unconditioned stimulus (US), typically footshock. This form of emotional learning is known to involve the convergence of auditory and somatosensory inputs onto single neurons in the lateral nucleus of the amygdala (LA), thereby initiating a cascade of molecular events involved in protein-synthesis, which is required for the formation of long-term memory (LTM). Traditional Pavlovian learning is generally assumed to involve the simultaneous overlapping presentation of two stimuli. Here, we sought to determine whether rats could acquire a persistent amygdala-dependent fear association when a footshock was cued by the explicit absence of a stimulus, rather than by a neutral tone. After habituation to the context, rats were given three presentations of either a 20-sec silence or a 20-sec tone (5kHz, 75dB), each of which coterminated with a mild footshock (0.5s, 0.8mA). In the silence condition, a constant 5kHz tone played in the background during inter-trial intervals, while in the tone condition, the background was silent. The next day, rats were tested for LTM in a novel context by presenting the appropriate training-CS in the absence of the US. The total duration of freezing to each 20-sec CS was used as a measure of fear reactivity. We found that after three silence-shock CS-US pairings, rats froze to silence as strongly as rats conditioned with tone-shock pairings froze to the tone. We then addressed whether the amygdala was necessary for the formation of these persistent silence-shock associations. Previous studies have found that the intra-LA infusion of U0126, an inhibitor of ERK/MAPK signaling, prior to fear conditioning, disrupts LTM but not short-term memory (STM). We infused U0126 (1.0µg in 0.25µL DMSO per side) directly into the LA 30 minutes before fear conditioning with the same 3-pairing silence-shock protocol, and then tested rats in a distinct context, first for STM at 3 hours post-training, and then for LTM, 48 hours later. Rats receiving U0126 prior to fear conditioning showed a significant attenuation of silence-induced fear LTM, but not STM, relative to DMSO vehicle controls. Further experiments will be necessary to elucidate the neural mechanisms that drive emotional learning about the absence of a stimulus.

Support Contributed By: NIH Grant R01 MH46516; NIH Grant R37 MH38774; NIH Grant K05 MH067048 ; NIH Grant P50 MH58911

Program No. 307.7/BBB20
Poster presentation:Sunday, Nov 04, 2007, 3:00 PM - 4:00 PM
Location: San Diego Convention Center: Halls B-H