State-dependent effect of dopamine D1/D5 receptors inactivation on memory destabilization and reconsolidation

Integration of New Information with Active Memory Accounts for Retrograde Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis?

“…Since 2000, several authors (who agree with the basic tenets of the consolidation/reconsolidation hypothesis), have provided evidence suggesting that, in the absence of amnesic treatment, active memories involve an adaptive process, allowing new information to be integrated within preexisting memories to update previous knowledge (Przybyslawski and Sara, 1997;Dudai and Eisenberg, 2004;Hupbach et al, 2007;Lee, 2009). Hence, the literature suggests that, depending on the type of information delivered while the memory is active, two different outcomes may happen.…”

“…According to Lewis (1979), memory can be distinguished as existing in one of two states: (1) an active but time-limited state, prevailing at the time of acquisition and reactivation; and (2) an inactive phase into which the active state transitions. During reactivation, older memories are brought back online and become labile, so that new information can be acquired, modifying and updating the initial memory (Przybyslawski and Sara, 1997;Lee, 2010). Importantly, labile does not necessarily refer to fragility but rather to malleability.…”

“…Typically, these results showing recovery of memory have been interpreted as revealing cases of state dependency induced by the amnesic agents, although drugs were administered after training (or reactivation), whereas in traditional state-dependent research, the drug is administered before training. Several authors suggested that memory itself was not lost but that amnesia resulted from retrieval difficulties attributable to a different state at training and testing (Quartermain et al, 1970;Miller and Springer, 1973;Millin et al, 2001). However, despite these criticisms and numerous others showing recovery after exposure to reminders, the consolidation hypothesis has remained: (1) because a fully convincing alternative explanation has never been proposed; and (2) because the consolidation was in agreement with results provided by molecular and cellular approaches of memory (Alberini, 2005;Tronson and Taylor, 2007).…”

“…The underly-ing neuronal processes required to stabilize memory have been conceptualized as a consolidation process (McGaugh, 1966). The finding that a similar amnesic phenomenon occurs after an old memory is reactivated (Misanin et al, 1968;Lewis, 1979) was later described as "reconsolidation" (Przybyslawski and Sara, 1997), involving processes similar to those in consolidation (Nader et al 2000), including de novo protein synthesis. An important element of both of these hypotheses is that the retrograde amnesia reflects the disruption of storage (or re-storage) of the memory.…”

“…An important implication is that reinstating the modified internal state at the time of testing should reverse amnesia. To investigate this possibility directly, we chose a protein synthesis inhibitor, cycloheximide (Cyclo), because protein synthesis inhibition can induce memory deficits in a time-dependent manner during consolidation or reconsolidation periods (Flood et al, 1972;Squire and Barondes, 1972;Quartermain and Botwinick, 1975;Nader et al, 2000;Alberini, 2008). Based on these previous studies, prevailing neuroscience theories state that the process of learning something novel initiates the synthesis of new proteins that participate in the processes of consolidation and reconsolidation of the memory.…”