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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 L-type voltage-gated Ca++ channels.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received a s.c. infusion of nimodipine (NIMO) or its vehicle (VEH), and, 30 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 = 8, VEH + DIST, N = 9, NIMO, N = 8, and NIMO + DIST, N = 8). (a) significantly different from both control groups, VEH and NIMO (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from all the other groups (P < 0.05; Newman-Keuls post-hoc test); (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).
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f3: Memory disruption is dependent on destabilization mediated by L-type voltage-gated Ca++ channels.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received a s.c. infusion of nimodipine (NIMO) or its vehicle (VEH), and, 30 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 = 8, VEH + DIST, N = 9, NIMO, N = 8, and NIMO + DIST, N = 8). (a) significantly different from both control groups, VEH and NIMO (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from all the other groups (P < 0.05; Newman-Keuls post-hoc test); (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).

Mentions: One necessary step in the reactivation/reconsolidation process is trace destabilization, which is mediated by L-type voltage-gated Ca++ channels: nimodipine, a selective LVGCC antagonist, can prevent it without affecting concomitant processes such as memory storage or retrieval (de Oliveira Alvares et al., 2013; Suzuki et al., 2008; Sierra et al., 2013; Cassini et al., 2013). Accordingly, if memory disruption caused by the distractor stimulus actually relies on a memory reconsolidation process, then nimodipine should prevent the effect (Fig. 3). ANOVA for Repeated Measures has shown a significant effect of group (F(3,29) = 28.3694 , P = 0.0000), drug (F(3,29) = 8.3980, P = 0.0071) and session*group interaction (F(3,29) = 11.7974, P = 0.0019), but not of session (F(3,29) = 2.3873, P = 0.1332), and the remaining interactions: session*drug (F(3,29) = 2.9146, P = 0.0985) and session*group*drug (F(3,29) = 1.4041, P = 0.2457). In the test session, Newman-Keuls post-hoc analysis has shown that only the VEH + DIST group expressed lower freezing levels compared to all the other groups, VEH (P = 0.02757), NIMO (P = 0.01535), or NIMO + DIST (P = 0.0168). In the reactivation session, however, both VEH + DIST and NIMO + DIST groups have shown lower freezing levels compared to the other groups, VEH (P = 0.0030 and 0.0348, respectively) and NIMO (P = 0.0015 and 0.0243, respectively (Newman-Keuls post-hoc analysis). The only group to present a significantly different performance between sessions was the NIMO + DIST one (P = 0.0014; 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 L-type voltage-gated Ca++ channels.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received a s.c. infusion of nimodipine (NIMO) or its vehicle (VEH), and, 30 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 = 8, VEH + DIST, N = 9, NIMO, N = 8, and NIMO + DIST, N = 8). (a) significantly different from both control groups, VEH and NIMO (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from all the other groups (P < 0.05; Newman-Keuls post-hoc test); (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

f3: Memory disruption is dependent on destabilization mediated by L-type voltage-gated Ca++ channels.(A) Schematic representation of the behavioral procedures: 48 h after training, rats received a s.c. infusion of nimodipine (NIMO) or its vehicle (VEH), and, 30 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 = 8, VEH + DIST, N = 9, NIMO, N = 8, and NIMO + DIST, N = 8). (a) significantly different from both control groups, VEH and NIMO (P < 0.05; Newman-Keuls post-hoc test); (b) significantly different from all the other groups (P < 0.05; Newman-Keuls post-hoc test); (c) performance differs significantly between sessions (P < 0.05; Newman-Keuls post-hoc test).
Mentions: One necessary step in the reactivation/reconsolidation process is trace destabilization, which is mediated by L-type voltage-gated Ca++ channels: nimodipine, a selective LVGCC antagonist, can prevent it without affecting concomitant processes such as memory storage or retrieval (de Oliveira Alvares et al., 2013; Suzuki et al., 2008; Sierra et al., 2013; Cassini et al., 2013). Accordingly, if memory disruption caused by the distractor stimulus actually relies on a memory reconsolidation process, then nimodipine should prevent the effect (Fig. 3). ANOVA for Repeated Measures has shown a significant effect of group (F(3,29) = 28.3694 , P = 0.0000), drug (F(3,29) = 8.3980, P = 0.0071) and session*group interaction (F(3,29) = 11.7974, P = 0.0019), but not of session (F(3,29) = 2.3873, P = 0.1332), and the remaining interactions: session*drug (F(3,29) = 2.9146, P = 0.0985) and session*group*drug (F(3,29) = 1.4041, P = 0.2457). In the test session, Newman-Keuls post-hoc analysis has shown that only the VEH + DIST group expressed lower freezing levels compared to all the other groups, VEH (P = 0.02757), NIMO (P = 0.01535), or NIMO + DIST (P = 0.0168). In the reactivation session, however, both VEH + DIST and NIMO + DIST groups have shown lower freezing levels compared to the other groups, VEH (P = 0.0030 and 0.0348, respectively) and NIMO (P = 0.0015 and 0.0243, respectively (Newman-Keuls post-hoc analysis). The only group to present a significantly different performance between sessions was the NIMO + DIST one (P = 0.0014; 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