*F. SOTRES-BAYON, L. DIAZ-MATAIX, D. E. A. BUSH, J. E. LEDOUX;
Ctr. Neural Sci., New York Univ., New York, NY

We recently demonstrated that both systemic and intra-amygdala blockade of NR2B-containing NMDA receptors (NMDARs) before extinction training, using ifenprodil, impairs the acquisition of fear extinction, and thereby its retrieval (Sotres-Bayon et al 2007). These results are consistent with the traditional notion that NMDARs are involved in learning-mediated plasticity. However several recent studies, using different learning tasks, have also reported effects of NMDA blockade on memory consolidation. Here we performed experiments involving post-extinction training treatments with ifenprodil to investigate the possibility that NR2B-containing NMDARs are required for the consolidation of extinction learning. In three experiments, we examined the effects of ifenprodil through systemic injections, and local microinfusions into the lateral amygdala (LA) and ventromedial prefrontal cortex (vmPFC) immediately after extinction training. Rats that were previously fear conditioned (7 tone-footshock pairings), were given systemic injections, bilateral intra-LA and midline intra-vmPFC infusions of ifenprodil (5mg/kg, 1µg/0.25µl/side and 2µg/0.5µl respectively) or vehicle immediately after fear extinction training. Also, to control for possible effects of NMDAR blockade in the vmPFC during extinction acquisition, another group of rats were given midline intra-vmPFC ifenprodil (2µg/0.5µl) or vehicle but before extinction training. Conditioned fear (freezing) to the tone was measured during fear conditioning, a day later within the extinction training session (20 tone-alone trials), and again a day later in the extinction retrieval test (5 tone-alone trials). We found that both systemic injection and intra-vmPFC infusions of ifenprodil immediately after extinction training impaired extinction retrieval; whereas pre-training intra-vmPFC had no effect on extinction acquisition or on its retrieval. These results confirm recent evidence showing that NMDARs in the vmPFC are involved in consolidation of the extinction memory, but not in its acquisition (Burgos-Robles et al 2007), and additionally show that vmPFC NR2B-containing NMDARs are required. Contrasting with the impairment seen with intra-LA ifenprodil given before extinction training in our earlier report, intra-LA ifenprodil given after extinction training did not significantly impair extinction retrieval. Overall, this indicates a double-dissociation between the role of LA and vmPFC NR2B-containing NMDA receptors, respectively, in the acquisition and consolidation of fear extinction

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