, 2011). Interestingly, application of glucocorticoid receptor agonists to mPFC immediately after training actually enhances inhibitory avoidance ( Roozendaal et al., 2009). The ventral

region of mPFC also plays a critical role in the consolidation of extinction of both fear and drug-related memories (Peters et al., 2009). Extinction is now known to be an active learning process involving the association between a conditioned stimulus and the absence of the unconditioned stimulus that was formerly associated with it. As with many other types of learning, disruption of synaptic plasticity in ventral mPFC after extinction training impairs memory for extinction of fear when tested 1–2 days later (Mamiya et al., 2009; Sotres-Bayon et al., 2009). Likewise, inhibiting mPFC after each daily Selleck Vorinostat extinction session leads to impaired extinction of drug craving (LaLumiere et al., 2010). Intriguingly, a recent study demonstrated GSK-3 activity enhanced fear extinction when the ventral mPFC was treated with a plasticity enhancing agent after extinction training ( Marek et al., 2011). There appears to be a critical window for consolidation in that chemical disruption of mPFC 1 to 2 hr after learning causes memory impairment whereas

disruption outside this window does not (Carballo-Márquez et al., 2007; Izaki et al., 2000; LaLumiere et al., 2010; Takehara-Nishiuchi et al., 2005; Tronel and Sara, 2003; see Table S1 available online). What is the nature of mPFC activity during this critical posttask period? Consolidation theory suggests that during off-line periods, most notably sleep, the hippocampus reactivates recently learned experiences which, in turn, causes replay of these events in the neocortex. Replay allows new memories to become integrated with previous cortical memories and hence, more robust to interference (i.e., “consolidated”) (McClelland et al., 1995). In support of this theory, spike patterns corresponding to task activity have been shown to replay in hippocampus much and several cortical areas during the rest period immediately following a task (Hoffman and McNaughton,

2002; Ji and Wilson, 2007; Wilson and McNaughton, 1994). Recently, robust replay has been observed in mPFC and an associated structure, the nucleus accumbens (Euston et al., 2007; Lansink et al., 2009). In both structures, replay occurs at an accelerated rate relative to that seen during behavior. Further, this replay is selective for recently learned events, suggesting a causal link in memory formation (Peyrache et al., 2009). A critical issue is whether replay in mPFC is orchestrated by the hippocampus. Considerable evidence suggests that it is. Reactivation in hippocampus is tied to local field potential features called “sharp waves” (Kudrimoti et al., 1999). Likewise, reactivation in mPFC is strongest during periods with a high density of field potential oscillations known as “low-voltage spindles” (Johnson et al., 2010).