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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 reactivation in the presence of a distractor disrupts fear memory expression in a long-lasting way.(A) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48 h after training (reactivation session); all groups were tested on day 5, and retested on day 20, in this same context. (B) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 12 or DIST – Distractor, N = 11). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures). (C) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48h after training (reactivation session); all groups were tested on day 5, exposed to unconditioned stimulus (reinstatement session) on day 6, and retest on day 7. (D) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 10 or DIST – Distractor, N = 8). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures).
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f1: Memory reactivation in the presence of a distractor disrupts fear memory expression in a long-lasting way.(A) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48 h after training (reactivation session); all groups were tested on day 5, and retested on day 20, in this same context. (B) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 12 or DIST – Distractor, N = 11). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures). (C) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48h after training (reactivation session); all groups were tested on day 5, exposed to unconditioned stimulus (reinstatement session) on day 6, and retest on day 7. (D) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 10 or DIST – Distractor, N = 8). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures).

Mentions: In our first experiment, we evaluate whether distractor stimulus was able to disrupt memory reconsolidation – a labile state that follows the reactivation that makes it susceptible to disruption (Nader et al., 2009). Rats were trained in the contextual fear conditioning (CFC) and later re-exposed to the same context (reactivation) in order to induce memory destabilization. In the distracted group, a soft air puff (the distractor stimulus) was applied to the animals during their freezing, while in the control group, reactivation did not involve any distractor stimulus. Animals were tested at 2 and retested at 20 days after training, in the same context (Fig. 1A,B). ANOVA for Repeated Measures revealed a significant effect of group (F(1,21) = 9.3929, P = 0.0059), but not of session (F(1,21) = 0.5431, P = 0.5850) or group*session interaction (F(1,21) = 0.0105, P = 0.9896): notice that DIST group exhibited less freezing than its control along all sessions. Additionally, other animals were retest after exposure to the unconditioned stimulus, i.e. reinstatement procedure (Fig. 1C,D). ANOVA for Repeated Measures showed a significant effect of group (F(1,16) = 29.4724, P = 0,0001), but not of session (F(1,16) = 1.9626, P = 0.15704) or group*session interaction (F(1,16) = 0.0324, P = 0.9682): demonstrating that freezing levels of DIST group was maintained in lower levels when compared to control during all sessions, even after unconditioned stimulus.


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 reactivation in the presence of a distractor disrupts fear memory expression in a long-lasting way.(A) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48 h after training (reactivation session); all groups were tested on day 5, and retested on day 20, in this same context. (B) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 12 or DIST – Distractor, N = 11). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures). (C) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48h after training (reactivation session); all groups were tested on day 5, exposed to unconditioned stimulus (reinstatement session) on day 6, and retest on day 7. (D) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 10 or DIST – Distractor, N = 8). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Memory reactivation in the presence of a distractor disrupts fear memory expression in a long-lasting way.(A) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48 h after training (reactivation session); all groups were tested on day 5, and retested on day 20, in this same context. (B) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 12 or DIST – Distractor, N = 11). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures). (C) Schematic representation of the behavioral procedures: rats were re-exposed to the fear conditioning context without the US (shock) 48h after training (reactivation session); all groups were tested on day 5, exposed to unconditioned stimulus (reinstatement session) on day 6, and retest on day 7. (D) Percent of freezing time during reactivation, test and retest sessions expressed as mean ± S.E.M. (CTR – Controls, N = 10 or DIST – Distractor, N = 8). (a) significantly different from respective control group (P < 0.05; effect of groups, ANOVA for Repeated Measures).
Mentions: In our first experiment, we evaluate whether distractor stimulus was able to disrupt memory reconsolidation – a labile state that follows the reactivation that makes it susceptible to disruption (Nader et al., 2009). Rats were trained in the contextual fear conditioning (CFC) and later re-exposed to the same context (reactivation) in order to induce memory destabilization. In the distracted group, a soft air puff (the distractor stimulus) was applied to the animals during their freezing, while in the control group, reactivation did not involve any distractor stimulus. Animals were tested at 2 and retested at 20 days after training, in the same context (Fig. 1A,B). ANOVA for Repeated Measures revealed a significant effect of group (F(1,21) = 9.3929, P = 0.0059), but not of session (F(1,21) = 0.5431, P = 0.5850) or group*session interaction (F(1,21) = 0.0105, P = 0.9896): notice that DIST group exhibited less freezing than its control along all sessions. Additionally, other animals were retest after exposure to the unconditioned stimulus, i.e. reinstatement procedure (Fig. 1C,D). ANOVA for Repeated Measures showed a significant effect of group (F(1,16) = 29.4724, P = 0,0001), but not of session (F(1,16) = 1.9626, P = 0.15704) or group*session interaction (F(1,16) = 0.0324, P = 0.9682): demonstrating that freezing levels of DIST group was maintained in lower levels when compared to control during all sessions, even after unconditioned stimulus.

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