, 2004; Mölle et al., 2006; Siapas and Wilson, 1998; Sirota et al., 2003). Further strengthening the link, sharp waves in hippocampus have recently been

shown to be correlated with memory replay in mPFC (Peyrache et al., 2009). The directionality find more of the mPFC-hippocampal interaction during sleep has been difficult to discern, with some results suggesting events in hippocampus precede those in cortex (Battaglia et al., 2004; Wierzynski et al., 2009) while others suggest the opposite (Isomura et al., 2006; Mölle et al., 2006). Perhaps both sides are correct. It has been suggested that cortical events initiate hippocampal replay, which in turn reinforces the ongoing replay of patterns in the neocortex (Sirota et al., 2003). Alternatively, the directionality of information flow from hippocampus to mPFC may depend on whether the information being processed is newly learned. One puzzling aspect of these consolidation findings is that tasks affected by posttask mPFC disruption are

not necessarily mPFC-dependent during initial learning. For example, odor-reward selleck screening library associations tested 48 hr after learning are impaired by consolidation block, yet rats with prelimbic lesions can easily acquire and retrieve odor-reward associations within a single session (Birrell and Brown, 2000; Tronel and Sara, 2003). Likewise, a NMDA antagonist injected into infralimbic cortex after extinction training interferes with the consolidation of fear extinction but NMDA receptor block during extinction training has no effect on within-session acquisition of extinction or subsequent recall ( Mamiya et al., 2009). Instrumental conditioning of lever pressing for food reward shows a similar pattern ( Izaki et al., 2000; Ostlund and Balleine, 2005) over as does object recognition ( Akirav and Maroun, 2006; Ennaceur et al., 1997). The framework presented here predicts that mPFC will be involved in initial acquisition, consolidation, and retrieval of context-event-response associations. Hence, it cannot fit these data without additional stipulations. One possible explanation is that other prefrontal cortical areas can compensate

for mPFC loss during learning but not during consolidation or recall. For example, aspects of odor-reward association may be mediated by both the OFC as well as ventral mPFC. If ventral mPFC is off-line during learning, OFC may become more heavily involved to the point that it can support learning independently. If mPFC is on-line during learning, however, the mPFC remains essential for consolidation and recall. Numerous research paradigms implicate mPFC in short-term memory, operationally defined here as memory spanning seconds to minutes. Historically, considerable emphasis has been placed on the role of mPFC in memory spanning intervals less than a minute, a capacity referred to as “working” memory (Uylings et al.