Based on the dual roles of CS alone presentation, Eisenberg et al. (2003) suggested that the effects of amnesic agents differ depending on whether the original memory trace or the

newly developed memory for extinction was dominant at the time of amnesic treatment. To test the trace dominance theory, subjects were given either more initial CS/US training or more CS-alone trials after initial conditioning, with the assumption that more initial training would cause the fear memory to dominate during the reminder, while extinction memory would dominate after more sessions with the CS alone. Consistent with the trace dominance hypothesis, more CS/US pairings resulted in disrupted reconsolidation of the original aversive memory whereas PARP inhibitor more CS-alone presentations resulted in subsequent loss of extinction and preserved fear memory, in different species and different memory tests. These findings can also explain why extensive training and/or specific time periods between initial training and reminder could result in strong, original memory

traces that are reactivated as dominant following a reminder (Suzuki et al., 2004, Wang et al., 2009, Milekic and Alberini, 2002, Eisenberg and Dudai, 2004 and Robinson and Franklin, 2010, but see Duvarci et al., 2006) and why effective reminders must be presented for reconsolidation of the original memory (Bozon et al., 2003). The other major factor in determining the efficacy of amnesic agents in the reconsolidation protocol GDC-0068 mw is whether the reminder event involves new learning in addition to recovery of the initial memory trace. One study reported that whereas original memories are blocked by an amnesic agent following a CS alone reminder, there was no loss of the original memory following reminder presentations that involve a combination of CS and US presentations, suggesting that CS alone reminder constituted a new learning experience

(Pedreira et al., 2004). However, there are several examples of successful disruption of reconsolidation following presentation of both a CS and US (Duvarci and Nader, 2004, Rodriguez-Ortiz et al., 2008 and Valjent et al., 2006). In these studies, it is not clear that performance was at asymptote, leaving open the possibility that new learning still occurred during others the reminder event, a factor that proved critical in another study (Rodriguez-Ortiz et al., 2005). Also, Morris et al. (2006) directly compared reconsolidation following reminder trials in rats trained to asymptotic performance in standard (“reference memory”) water maze task versus a (“working memory”) variant of the task where new escape locations were learned daily and found that anisomycin was effective after reminders only in the condition of new learning each day. Also, in other studies on human declarative and motor memory, providing subjects with a reminder that involves new learning is key to alteration of existing memories (Walker et al., 2003, Hupbach et al.