*F. SOTRES-BAYON, D. E. BUSH, J. E. LEDOUX;
Center for Neural Science, New York University, New York, NY.

N-methyl-D-asparate receptors (NMDARs) contribute to the synaptic plasticity that underlies learning and memory in a variety of brain systems. Fear conditioning, which is known to involve plasticity within the amygdala, depends on NMDARs that contain the NR2B subunit. Fear extinction, which involves learning to inhibit a previously acquired fear response, also appears to require NMDA-dependent plasticity in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning or the ability to consolidate the extinction memory. Recently, we showed that systemic blockade of NR2B-containing NMDARs before extinction training, using ifenprodil, impairs fear extinction acquisition, and thus its retrieval. In the present study, we examined the effects of ifenprodil infused locally into the lateral amygdala prior to extinction training. Rats that had previously undergone auditory fear conditioning (7 tone-footshock pairings) were given intra-amygdala microinjections of vehicle or ifenprodil, one day after fear acquisition and 15-45 min prior to fear extinction training. Conditioned fear (freezing) to the tone was measured within the initial extinction training session (20 tone-alone presentations), and again 24 h later (5 tone-alone presentations). We found that intra-amygdala blockade of NR2B-containing NMDARs with ifenprodil significantly impaired extinction learning on the first day of extinction, which was also associated with impaired extinction retrieval the next day. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only in the retention, of fear extinction learning.
Support Contributed By: R01 MH046516;R37 MH38774;K05 MH067048;R21 MH072279

Program No. 370.4/KK22
Poster presentation:Monday, Oct 16, 2006, 11:00 AM -12:00 PM
Location: Georgia World Congress Center: Halls B3-B5