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

Abstract

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).

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

“…One is that tDCS allowed modulation, albeit small, during a window of opportunity immediately after fear extinction learning on extinction consolidation when the extinction memory is still in a short‐term, labile state (McGaugh, 2000). Support for this idea can be found in animal studies where inactivation of the rodent vmPFC immediately after extinction training impaired memory for extinction (Burgos‐Robles, Vidal‐Gonzalez, Santini, & Quirk, 2007; Hikind & Maroun, 2008; Laurent & Westbrook, 2008; Sotres‐Bayon, Diaz‐Mataix, Bush, & LeDoux, 2009). Furthermore, extinction success is associated with the amount of high frequency bursting in rodent vmPFC neurons during (Chang, Berke, & Maren, 2010) as well as after extinction training (Burgos‐Robles et al., 2007).…”

The Basolateral Amygdala Is Critical for the Acquisition and Extinction of Associations between a Neutral Stimulus and a Learned Danger Signal But Not between Two Neutral Stimuli

“…The neural circuitry underling first-order fear inhibition involves interactions among several structures, including the BLA and the infralimbic (IL) subregion of the medial prefrontal cortex. Specifically, the IL appears necessary for the consolidation and retrieval of first-order fear extinction but not its acquisition (Laurent and Westbrook, 2009;Sotres-Bayon et al, 2009). The IL is likely to suppress fear responses via excitatory projections to "extinction" neurons in the BLA (Herry et al, 2008) and to a network of inhibitory interneurons (intercalated neurons) located between the BLA and CeA (Paré and Smith, 1993;Quirk and Mueller, 2008).…”

The selectivity of aversive memory reconsolidation and extinction processes depends on the initial encoding of the Pavlovian association

“…Neurons in the lateral nucleus of the amygdala (LA) play a critical role in memory acquisition, consolidation, storage, retrieval, reconsolidation, and extinction (Sotres-Bayon et al 2009;Johansen et al 2011;Maren 2011).…”