Protein synthesis underlies post-retrieval memory consolidation to a restricted degree only when updated information is obtained

Abstract

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here we show that intracortical blockade of protein synthesis in the gustatory cortex after retrieval of taste-recognition memory disrupts previously consolidated memory to a restricted degree only if the experience is updated. Our results suggest that retrieved memory can be modified as part of a mechanism for incorporating updated information into previously consolidated memory.The memory consolidation hypothesis has been the major theoretical framework to explain long-term memory storage (McGaugh 1966(McGaugh , 2000. However, it has been reported that memory activated by retrieval becomes susceptible to disruption by the same means that disrupt consolidation (Misanin et al. 1968;Nader et al. 2000). This process, called reconsolidation, suggests that consolidated memory returns to a labile state similar to recently acquired memory each time it is retrieved (Sara 2000; Debiec et al. 2002). However, most of the studies in which reconsolidation process is achieved have used associative learning tasks requiring the association between a conditioned stimulus (CS) and an unconditioned stimulus (US) followed by extinction trials in which the CS is no longer followed by the US. Therefore, during retrieval, when reconsolidation is assessed, there is a competition between the extinction (CS-noUS) and the associative (CS-US) traces, which both require protein synthesis to be retained in long-term memory (Eisenberg et al. 2003;Pedreira and Maldonado 2003). Here we address the post-retrieval consolidation issue on a taste-recognition memory task that allows us to access the formation of memory in the absence of extinction. That is, we used a CS with the same valence during acquisition and retrieval so extinction does not occur and a competition between memories is not established.Animals exposed to novel taste show reduced consumption (neophobic response). This is followed by graded increases in intake after repeated presentations of the same tastant until a plateau is reached. This behavior is called attenuation of neophobia or AN (Domjan 1977;Buresova and Bures 1980; de VosKorthals and van Hof 1984;Dogterom and van Hof 1988;Bermudez-Rattoni 2004). AN is a long-lasting behavior in which animals must remember a taste as having been experienced previously. This kind of memory is referred as taste-recognition memory (Bermudez-Rattoni 2004), and the insular cortex (IC) (the gustatory neocortex) has been proven to be an important site of gustatory memory formation (Rosenblum et al. 1993; Gutierrez et al. 2003a,b;Bermudez-Rattoni 2004). In AN, the animal exposed to a particular taste will drink more of that solution regardless of the time elapsed between two consecutive taste presentatio...

Cholinergic manipulations bidirectionally regulate object memory destabilization

“…We predicted a key role for cholinergic transmission in memory destabilization because of the common finding that reconsolidation is prompted most reliably when novel information is available during the reactivation episode (Rodriguez-Ortiz et al 2005;Morris et al 2006;Rossato et al 2007;Winters et al 2009;Forcato et al 2010;Sevenster et al 2013). Indeed, ACh has long been implicated in cognitive functions linked to new learning (Sarter and Bruno 1997;Hasselmo and McGaughy 2004), and in vivo microdialysis studies demonstrate enhanced ACh release in various brain regions when animals explore novel environments or objects (Tang and Aigner 1996;Aloisi et al 1997;Giovannini et al 2001;Ihalainen et al 2010) or are otherwise aroused (Nilsson et al 1990;Inglis and Fibiger 1995) or attentionally taxed (Passetti et al 2000).…”

“…Indeed, not all memories become labile when reactivated; boundary conditions, including the strength of initial memory encoding and the age of the memory at the time of retrieval, determine the likelihood of destabilization upon reactivation (Milekic and Alberini 2002;Eisenberg and Dudai 2004;Suzuki et al 2004;Winters et al 2009). These boundary conditions may be related to the putative role of reconsolidation in memory updating (Sara 2000;Rodriguez-Ortiz et al 2005;Morris et al 2006;Hupbach et al 2007;Rossato et al 2007;Lee 2009;Forcato et al 2010;Sevenster et al 2013). Accordingly, stronger or more remote memories may be less likely to be altered in the absence of salient novel information (Lee 2009;Winters et al 2009).…”

Characterization of spatial memory reconsolidation

“…However, in these experiments the cortical transfer occurred 3 -4 wk after the initial acquisition. As we have already mentioned, a well-learned memory does not undergo reconsolidation unless in the presence of new information to update it (Rodriguez-Ortiz et al 2005;Morris et al 2006;Winters et al 2009). However, the possible involvement of neocortical regions in the case of strong hippocampus-independent memories has never been explored in the case of spatial memory reconsolidation.…”

“…Even though Tronel et al (2005) concluded that reconsolidation was not required to link new information to a retrieved memory, Lee (2008) demonstrated that an adaptive function of the reconsolidation process enables the update of memory's content. Without the presence of new information, thus when updating is not necessary, a very well-learned memory does not undergo reconsolidation (Rodriguez-Ortiz et al 2005;Winters et al 2009). …”

Familiar taste induces higher dendritic levels of activity-regulated cytoskeleton-associated protein in the insular cortex than a novel one

“…Behaviorally, safe taste memory trace formation is observed by a gradual increase in the intake of flavored-water solution as a function of the number and the duration of prior periods of access to the solution and it was termed Attenuation of Neophobia (AN) (Domjan 1976) or safe Taste Recognition Memory (Bermudez-Rattoni 2004). Taste familiarization has been shown to be a gradual, updatable process dependent on several rounds of protein synthesis in the IC upon reactivation (Rodriguez-Ortiz et al 2005). Also, it has been shown with a number of distinct methods that the activity of tasteresponsive neurons in the IC can be modified with learning (Yasoshima and Yamamoto 1998;Bahar et al 2004;Accolla and Carleton 2008).…”