Intrahippocampal anisomycin infusions disrupt previously consolidated spatial memory only when memory is updated

Rodriguez‐Ortiz, Carlos J.; García-delaTorre, Paola; Benavidez, Eduardo; Ballesteros, María Ángeles; Bermúdez-Rattoni, Federico

doi:10.1016/j.nlm.2007.10.004

Cited by 67 publications

(42 citation statements)

References 36 publications

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“…This idea is supported by a differential effect of 4EGI-1 on consolidation and reconsolidation and by biochemical data showing that eIF4E-eIF4G interactions are enhanced following initial fear conditioning but not following memory reactivation. These results diverge from previous studies with general protein synthesis inhibitors, such as anisomycin and CHX (12,28), but are consistent with the recent reports of biochemical differences between consolidation and reconsolidation (29,30). The specificity of 4EGI-1 for eIF4E-eIF4G interactions enabled us to use substantially lower drug concentrations than previous studies with anisomycin, which likely results in complete blockade of translation, but also nonspecific and cytotoxic effects (14).…”

Section: Resultssupporting

confidence: 75%

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation

Hoeffer

Cowansage

Arnold

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

111

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Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intraamygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory. T he synthesis of new proteins within relevant neuronal circuits is widely agreed to be a basic requirement for long-term memory (LTM) storage. Translation is important for stabilizing active memories because it triggers the production of new proteins that are required for persistent molecular and synaptic changes during both consolidation (after learning) and reconsolidation (after memory reactivation). However, the role of translation in memory formation has been explored only in the context of overall cellular protein translation. There are at least two forms of protein synthesis that could in principle be exploited for either memory consolidation or reconsolidation. The primary mode of translation initiation requires formation of a multiprotein complex of eukaryotic initiation factors (eIFs) bound to the 5′ methylated-GTP cap of target mRNAs (1, 2). Specifically, the interaction between eIF4E and eIF4G facilitates eIF4A RNA helicase activity, recruitment of the 40S ribosomal subunit, scanning, and peptide elongation (3, 4). Molecules that block the formation of eIF4F (eIF4E + eIF4G + eIF4A), such as the endogenous regulator 4E-binding protein, which binds to and sequesters eIF4E, therefore effectively inhibits cap-dependent translation. Likewise, the small molecule, 4EGI-1, which selectively disrupts eIF4E-eIF4G interactions (eIF4F formation) in vitro (5), also inhibits cap-dependent translation. The second route that mRNAs can be translated occurs via internal ribosomal entry sites (IRES), which are unaffected by disruptions to the 5′ cap translation machinery, such as blockade of eIF4E-eIF4G interactions (5). A role for eIF4E-eIF4G interactions during hippocampal synaptic plasticity has been shown (6-8), but they have not yet been demonstrated for memory formation. The ability to dissociate mechanisms of translation control is relevant to the study of associative learning because little is known about the relative roles of cap-dependent and IRES-mediated translation in mammalian brain function. For example, there is evidence that an IRES mediates translation of fragile X mental retardation protein, a protein that is absent in ...

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Section: Resultssupporting

confidence: 75%

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation

Hoeffer

Cowansage

Arnold

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

101

111

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“…For example, post-retrieval injections of anisomycin into the hippocampus of rats trained on spatial tasks in the water maze resulted in subsequent memory impairment only when encoding of new information took place during retrieval (Morris et al 2006). This study and others (Rossato et al 2006;Rodriguez-Ortiz et al 2008) have shown that the hippocampus is critical for updating spatial memories. Taste recognition (Rodriguez-Ortiz et al 2005) and object recognition (Rossato et al 2007) paradigms have also found evidence that reconsolidation is involved in updating memories with new information.…”

supporting

confidence: 65%

“…The hippocampus has been shown to be critical for reconsolidation of spatial memories (Morris et al 2006;Rossato et al 2006;Rodriguez-Ortiz et al 2008). In our study, the Reminder group learned the first and second lists of feeders in the presence of the same configuration of contextual cues, whereas the No Reminder group learned the first and second lists in the presence of different configurations of cues.…”

Section: Discussionmentioning

confidence: 99%

Remaking memories: Reconsolidation updates positively motivated spatial memory in rats

Jones¹,

Bukoski²,

Nadel³

et al. 2012

Learn. Mem.

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There is strong evidence that reactivation of a memory returns it to a labile state, initiating a restabilization process termed reconsolidation, which allows for updating of the memory. In this study we investigated reactivation-dependent updating using a new positively motivated spatial task in rodents that was designed specifically to model a human list-learning paradigm. On Day 1, rats were trained to run to three feeders (List 1) for rewards. On Day 2, rats were trained to run to three different feeders (List 2) in either the same (Reminder condition) or a different (No Reminder condition) experimental context than on Day 1. On Day 3, rats were cued to recall List 1. Rats in the Reminder condition made significantly more visits to List 2 feeders (intrusions) during List 1 recall than rats in the No Reminder condition, indicating that the reminder triggered reactivation and allowed integration of List 2 items into List 1. This reminder effect was selective for the reactivated List 1 memory, as no intrusions occurred when List 2 was recalled on Day 3. No intrusions occurred when retrieval took place in a different context from the one used at encoding, indicating that the expression of the updated memory is dependent upon the retrieval context. Finally, the level of intrusions was highest when retrieval took place immediately after List 2 learning, and generally declined when retrieval occurred 1 -4 h later, indicating that the List 2 memory competed with short-term retrieval of List 1. These results demonstrate the dynamic nature of memory over time and the impact of environmental context at different stages of memory processing.Memories do not remain stable once acquired but, rather, change dynamically over one's lifetime. There is now strong evidence that reactivation of a memory (remembering) returns it to a labile state for a time, initiating a restabilization process that can allow for updating of the memory. This restabilization process, termed "reconsolidation," has been found to occur across a wide range of species and memory paradigms (Tronson and Taylor 2007; Nader and Einarsson 2010).There is evidence in both humans and animals that new information available when a memory is reactivated can modify that memory as a consequence of reconsolidation. In a human procedural memory study, brief rehearsal of a consolidated fingertapping sequence prior to learning a new sequence resulted in impairment of the original memory when subjects were tested 24 h later (Walker et al. 2003). Critically, no impairment was observed if the original sequence was not rehearsed prior to learning the new sequence, indicating that reactivation affected the memory for the original sequence in such a way that subsequent learning could disrupt it.It has recently been demonstrated in humans that reconsolidation can also be a constructive process, serving to update memories with new information . In this study, participants learned a list (List 1) of 20 objects on Day 1. On Day 2, the Reminder group was asked to recall the genera...

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“…Under certain circumstances, for instance, new information can be updated into the original trace and its strength can be significantly modified (Lee 2008(Lee , 2010Rodriguez-Ortiz et al 2008;Hupbach et al 2009). Hence, the combination of the retrieval experience and stress is functionally suitable to rewrite emotional memories readjusting the trace to contemporary environmental conditions (Schiller et al 2010).…”

mentioning

confidence: 99%

A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace

et al. 2013

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The present study investigates the fear memory resulting from the interaction of a stressful experience and the retrieval of an established fear memory trace. Such a combination enhanced both fear expression and fear retention in adult Wistar rats. Likewise, midazolam intra-basolateral amygdala (BLA) infusion prior to stress attenuated the enhancement of fear memory thus suggesting the involvement of a stress-induced reduction of the GABAergic transmission in BLA in the stress-induced enhancing effect. It has been suggested that, unlike the immediate-early gene Zif268 which is related to the reconsolidation process, the expression of hippocampal brain-derived neurotrophic factor (BDNF) is highly correlated with consolidation. We therefore evaluate the relative contribution of these two neurobiological processes to the fear memory resulting from the above-mentioned interaction. Intra-dorsal hippocampus (DH) infusions of either the antisense Zif268 or the inhibitor of the protein degradation (Clasto-Lactacystin b-Lactone), suggested to be involved in the retrieval-dependent destabilization process, did not affect the resulting contextual memory. In contrast, the knockdown of hippocampal BDNF mitigated the stress-induced facilitating influence on fear retention. In addition, the retrieval experience elevated BDNF level in DH at 60 min after recall exclusively in stressed animals. These findings suggest the involvement of a hippocampal BDNF sensitive mechanism in the stress-promoting influence on the fear memory following retrieval.

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Intrahippocampal anisomycin infusions disrupt previously consolidated spatial memory only when memory is updated

Cited by 67 publications

References 36 publications

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation

Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation

Remaking memories: Reconsolidation updates positively motivated spatial memory in rats

A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace

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