36-40 Hence, mPFC is in a position to inhibit the amygdala, a possible extinction mechanism,41 at least under some circumstances.42,43 Electrolytic lesions44 or localized inactivation45 of the infralimbic region of mPFC impair extinction retention while having little to no effect on acquisition or within-session extinction, suggesting a role for this region specifically in consolidation and/or expression of extinction memory (see also ref 46). Inhibitors,research,lifescience,medical Single units within infralimbic cortex fire selectively to presentations of a previously fear-conditioned cue during

an extinction retention test 24 h after extinction training but not during the extinction training session itself.47 When infralimbic cortex microstimulation was paired with presentations of

a previously fear conditioned cue in nonextinguished animals, freezing to those cues was attenuated, and this effect was also seen the next day when no stimulation was given.47,48 Collectively, Inhibitors,research,lifescience,medical these findings indicate that mPFC plays a significant role in many cases in extinction memory consolidation and expression, likely via its interactions with the amygdala. NMDA receptors within amygdala seem to be involved in the initiation of extinction, whereas Inhibitors,research,lifescience,medical in infralimbic cortex, they seem to be involved in consolidation of extinction. Microinfusions of NMDA see more receptor antagonists into basolateral nucleus of the amygdala prior to fear extinction training impair both within-session extinction and extinction retention.16,23,30,31,33 Inhibitors,research,lifescience,medical However, local infusions of NMDA 2A, 2B antagonists into basolateral amygdala block the expression of several fear-related conditioned responses, including freezing, suggesting these drugs could artifactually block extinction retention by interfering with synaptic transmission. However, infusion of ifenprodil, a drug that blocks a subtype of the NMDA receptor but does not block expression

of Inhibitors,research,lifescience,medical fear conditioned responses, still blocked extinction retention.28,30,31 Immediate post-extinction training infusions into the amygdala of ifenprodil have no effect on subsequent extinction retention when extinction of fear is measured.27,30 This suggests that NMDA receptor-dependent synaptic plasticity within amygdala is involved in encoding extinction of fear, but Thymidine kinase that the subtype of the NMDA receptor where ifenprodil acts in the amygdala is not required for consolidation of extinction, at least for conditioned fear. In contrast, pre-extinction training infusions of NMDA receptor antagonists into mPFC have no effect on within-session extinction but generally impair later extinction retention29,31,49; (but see ref 27). Immediate postextinction infusions of NMDA antagonists into the infralimbic cortex do block extinction retention consistently,27,29-31 providing strong evidence that NMDA receptor-dependent synaptic plasticity within this cortical area is involved primarily in consolidation of extinction memory.