Limits...
Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation.

Crestani AP, Zacouteguy Boos F, Haubrich J, Ordoñez Sierra R, Santana F, Molina JM, Cassini Lde F, Alvares Lde O, Quillfeldt JA - Sci Rep (2015)

Bottom Line: Both treatments were able to prevent the disruptive effect of distraction.Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon.Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way.

View Article: PubMed Central - PubMed

Affiliation: Psychobiology and Neurocomputation Lab, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way.

No MeSH data available.


Related in: MedlinePlus

Memory disruption is dependent on destabilization mediated by GluN2B-containing NMDA receptors in the hippocampus.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received an intrahippocampal (CA1 area) infusion of ifenprodil (IFEN) or its vehicle (VEH), and, 15 min later, were re-exposed to the fear conditioning context without the US (shock) – the Reactivation session – either with or without the presence of a distractor (DIST); all groups were tested on day 5. (B) Percent of freezing time during Reactivation and Test sessions expressed as mean ± S.E.M. (VEH, N = 9, VEH + DIST, N = 13, IFEN, N = 12, and IFEN + DIST, N = 12). (a) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); in both sessions, there is no significant difference among the remaining (unmarked) groups; (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556962&req=5

f4: Memory disruption is dependent on destabilization mediated by GluN2B-containing NMDA receptors in the hippocampus.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received an intrahippocampal (CA1 area) infusion of ifenprodil (IFEN) or its vehicle (VEH), and, 15 min later, were re-exposed to the fear conditioning context without the US (shock) – the Reactivation session – either with or without the presence of a distractor (DIST); all groups were tested on day 5. (B) Percent of freezing time during Reactivation and Test sessions expressed as mean ± S.E.M. (VEH, N = 9, VEH + DIST, N = 13, IFEN, N = 12, and IFEN + DIST, N = 12). (a) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); in both sessions, there is no significant difference among the remaining (unmarked) groups; (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).

Mentions: Trace destabilization was also shown to depend on NMDA receptors containing the GluN2B subunit (Ben Mamou et al., 2006; Milton et al., 2013; Haubrich et al., 2015), particularly in the hippocampus, a brain structure involved in contextual fear memory reconsolidation (Anagnostaras et al., 2001; Rudy, et al., 2004; Winocur et al., 2009). Thus, we infused the selective GluN2B antagonist ifenprodil bilaterally into the CA1 hippocampal area 15 min prior to reactivation session aiming to prevent memory destabilization, and, thus, gather support for the reconsolidation hypothesis (Fig. 4). ANOVA for Repeated Measures has shown a significant effect of group (F(3,42) = 17.0813, P = 0.0002), session (F(3,42) = 26.1011, P = 0.0000) and group*drug interaction (F(3,42) = 8.5353, P = 0.0056), but not of drug (F(3,42) = 0.2191, P = 0.6421), or the following interactions: session*group (F(3,42) = 1.6320, P = 0.2084), session*drug (F(3,42) = 4.0118, P = 0.0517) and session*group*drug (F(3,42) = 0.0454, P = 0.8323). In the test session, Newman-Keuls post-hoc analysis has shown that the VEH + DIST group expressed lower freezing levels compared to the VEH (P = 0.0326), but not to the remaining groups (P = 0.0987 and 0.0815, respectively). In the reactivation session, Newman-Keuls post-hoc analysis revealed that both VEH + DIST and IFEN + DIST groups were significantly smaller than the VEH control (P = 0.0032 and 0.0248, respectively), that, on its turn, was similar to IFEN (P = 0.5072). Similar to the nimodipine experiment, IFEN + DIST was the only group to present a significantly different performance between sessions (P = 0.0010; Newman-Keuls post-hoc test).


Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation.

Crestani AP, Zacouteguy Boos F, Haubrich J, Ordoñez Sierra R, Santana F, Molina JM, Cassini Lde F, Alvares Lde O, Quillfeldt JA - Sci Rep (2015)

Memory disruption is dependent on destabilization mediated by GluN2B-containing NMDA receptors in the hippocampus.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received an intrahippocampal (CA1 area) infusion of ifenprodil (IFEN) or its vehicle (VEH), and, 15 min later, were re-exposed to the fear conditioning context without the US (shock) – the Reactivation session – either with or without the presence of a distractor (DIST); all groups were tested on day 5. (B) Percent of freezing time during Reactivation and Test sessions expressed as mean ± S.E.M. (VEH, N = 9, VEH + DIST, N = 13, IFEN, N = 12, and IFEN + DIST, N = 12). (a) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); in both sessions, there is no significant difference among the remaining (unmarked) groups; (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556962&req=5

f4: Memory disruption is dependent on destabilization mediated by GluN2B-containing NMDA receptors in the hippocampus.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received an intrahippocampal (CA1 area) infusion of ifenprodil (IFEN) or its vehicle (VEH), and, 15 min later, were re-exposed to the fear conditioning context without the US (shock) – the Reactivation session – either with or without the presence of a distractor (DIST); all groups were tested on day 5. (B) Percent of freezing time during Reactivation and Test sessions expressed as mean ± S.E.M. (VEH, N = 9, VEH + DIST, N = 13, IFEN, N = 12, and IFEN + DIST, N = 12). (a) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from its control group, VEH (P < 0.05; Newman-Keuls post-hoc test); in both sessions, there is no significant difference among the remaining (unmarked) groups; (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).
Mentions: Trace destabilization was also shown to depend on NMDA receptors containing the GluN2B subunit (Ben Mamou et al., 2006; Milton et al., 2013; Haubrich et al., 2015), particularly in the hippocampus, a brain structure involved in contextual fear memory reconsolidation (Anagnostaras et al., 2001; Rudy, et al., 2004; Winocur et al., 2009). Thus, we infused the selective GluN2B antagonist ifenprodil bilaterally into the CA1 hippocampal area 15 min prior to reactivation session aiming to prevent memory destabilization, and, thus, gather support for the reconsolidation hypothesis (Fig. 4). ANOVA for Repeated Measures has shown a significant effect of group (F(3,42) = 17.0813, P = 0.0002), session (F(3,42) = 26.1011, P = 0.0000) and group*drug interaction (F(3,42) = 8.5353, P = 0.0056), but not of drug (F(3,42) = 0.2191, P = 0.6421), or the following interactions: session*group (F(3,42) = 1.6320, P = 0.2084), session*drug (F(3,42) = 4.0118, P = 0.0517) and session*group*drug (F(3,42) = 0.0454, P = 0.8323). In the test session, Newman-Keuls post-hoc analysis has shown that the VEH + DIST group expressed lower freezing levels compared to the VEH (P = 0.0326), but not to the remaining groups (P = 0.0987 and 0.0815, respectively). In the reactivation session, Newman-Keuls post-hoc analysis revealed that both VEH + DIST and IFEN + DIST groups were significantly smaller than the VEH control (P = 0.0032 and 0.0248, respectively), that, on its turn, was similar to IFEN (P = 0.5072). Similar to the nimodipine experiment, IFEN + DIST was the only group to present a significantly different performance between sessions (P = 0.0010; Newman-Keuls post-hoc test).

Bottom Line: Both treatments were able to prevent the disruptive effect of distraction.Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon.Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way.

View Article: PubMed Central - PubMed

Affiliation: Psychobiology and Neurocomputation Lab, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way.

No MeSH data available.


Related in: MedlinePlus