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Cerebral Cortex Advance Access published online on June 17, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn099
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Dissociable Roles for the Ventromedial Prefrontal Cortex and Amygdala in Fear Extinction: NR2B Contribution

Francisco Sotres-Bayon, Llorenç Diaz-Mataix, David E. A. Bush and Joseph E. LeDoux

Center for Neural Science, New York University, New York, NY 10003, USA

Address correspondence to Francisco Sotres-Bayon, PhD, Department of Psychiatry, University of Puerto Rico School of Medicine, PO Box 365067, San Juan, Puerto Rico 00936-5067. Email: fsotresb{at}gmail.com.

Fear extinction, which involves learning to suppress the expression of previously learned fear, requires N-methyl-D-aspartate receptors (NMDARs) and is mediated by the amygdala and ventromedial prefrontal cortex (vmPFC). Like other types of learning, extinction involves acquisition and consolidation phases. We recently demonstrated that NR2B-containing NMDARs (NR2Bs) in the lateral amygdala (LA) are required for extinction acquisition, but whether they are involved in consolidation is not known. Further, although it has been shown that NMDARs in the vmPFC are required for extinction consolidation, whether NR2Bs in vmPFC are involved in consolidation is not known. In this report, we investigated the possible role of LA and vmPFC NR2Bs in the consolidation of fear extinction using the NR2B-selective antagonist ifenprodil. We show that systemic treatment with ifenprodil immediately after extinction training disrupts extinction consolidation. Ifenprodil infusion into vmPFC, but not the LA, immediately after extinction training also disrupts extinction consolidation. In contrast, we also show pre-extinction training infusions into vmPFC has no effect. These results, together with our previous findings showing that LA NR2Bs are required during the acquisition phase in extinction, indicate a double dissociation for the phase-dependent role of NR2Bs in the LA (acquisition, not consolidation) and vmPFC (consolidation, not acquisition).

Key Words: conditioning • infralimbic • learning • NMDA • plasticity • prelimbic


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