, 2006). However, other studies showed that hippocampal reconsolidation is necessary for consolidated memories (Debiec et al., 2002 and Winocur et al., 2009), and a recent experiment on remote memories showed that the generalized, “semantic,” fear responding that normally occurs in nonconditioned contexts was also dependent on hippocampal reconsolidation (Winocur et al., 2009). Therefore, somehow pre-existing semantic networks must become hippocampus dependent, a condition that counters predictions of the original theory (Nadel and Moscovitch, 1997). In the schema modification model, consolidation Ibrutinib supplier occurs by integrating the new memory

into active, pre-existing memories via reorganization of common elements within the hippocampus and the cortex (Figures 1G and 1H). In reconsolidation experiments, the reminder determines which memories will this website be active during encoding and therefore which synapses will be affected by the new learning (Figure 1G). In this model, systemic amnesic treatment after a reminder would result in a partial integration of the newly learned information into the hippocampal and cortical networks, resulting in a corruption of the reorganizing network (Figure 1I, red). Manipulations limited to the hippocampus could cause disruption of cortical reconsolidation due to interrupted replay of the newly

acquired learning (Eichenbaum, 2006) or errant discharges Thymidine kinase from a damaged hippocampus driving molecular changes in reorganizing cortical circuits (Rudy and Sutherland, 2008) or perhaps another mechanism that would affect cortical circuits undergoing plastic remodeling. While each of the models described here captures some of the phenomenology of reconsolidation experiments, none has compelling support, and this is likely to remain the case until we better understand the nature of neural representations in the hippocampus and cortex and how they change during consolidation and its breakdown. While the cellular substrates of consolidation and reconsolidation

are largely shared, several studies have reported dissociations between these processes for particular plasticity molecules or for plasticity in general within certain brain regions (e.g., von Hertzen and Giese, 2005, Maroun and Akirav, 2009, Taubenfeld et al., 2001, Lee et al., 2004, Lee, 2008 and Lee, 2010; reviewed in Alberini 2005). Furthermore, several reconsolidation studies have shown that as time passes memories become resistant to reconsolidation blockers (Milekic and Alberini, 2002, Suzuki et al., 2004 and Eisenberg and Dudai, 2004), though others have found conflicting results (Debiec et al., 2002, Wang et al., 2009 and Robinson and Franklin, 2010). The apparent differences between consolidation and reconsolidation can be expected due to the design of consolidation experiments.