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Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze.

Kim R, Moki R, Kida S - Mol Brain (2011)

Bottom Line: We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory.Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription.We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.

ABSTRACT

Background: Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory.

Results: We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1) and L-type voltage gated calcium channels (LVGCCs) in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis.

Conclusions: Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

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Effect of no re-exposure on the stability of spatial memory. (A) Experimental design. (B) Probe trial at day 4 (VEH, n = 9; ANI, n = 9). *P < 0.05, time spent in the TQ vs. time spent in the other quadrants by post hoc Newman-Keuls test after significant one-way ANOVA. Error bars are SEM. Time spent (s) in target (T), adjacent left (L), adjacent right (R), and opposite (O) quadrants during the probe trial is shown.
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Figure 3: Effect of no re-exposure on the stability of spatial memory. (A) Experimental design. (B) Probe trial at day 4 (VEH, n = 9; ANI, n = 9). *P < 0.05, time spent in the TQ vs. time spent in the other quadrants by post hoc Newman-Keuls test after significant one-way ANOVA. Error bars are SEM. Time spent (s) in target (T), adjacent left (L), adjacent right (R), and opposite (O) quadrants during the probe trial is shown.

Mentions: As a control experiment, we examined whether the disruption of spatial memory by protein synthesis inhibition depends on memory reactivation at Re-exposure (PT 1). We performed a similar experiment as in Figure 2, except that mice were not given PT 1 (No Re-exposure). However, mice were micro-infused with ANI or VEH into the dorsal hippocampus at 24 h after training on day 2. Both groups of mice showed comparable memory performance and a progressive loss of escape latencies during training (days 1 and 2) (data not shown). In contrast to the results shown in Figure 2, VEH- and ANI-infused mice searched selectively in the TQ in the probe test (VEH, F3,32 = 16.485, P < 0.05; ANI, F3,32 = 10.108, P < 0.05) (Figure 3). ANI-infused mice showed comparable searching scores in the TQ as the VEH group (F1,16 = 0.002, P > 0.05). These results indicated that the inhibition of protein synthesis failed to disrupt spatial memory when the memory was not reactivated by the Re-exposure session, suggesting that the amnesic effects of ANI are contingent on the reactivation of spatial memory.


Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze.

Kim R, Moki R, Kida S - Mol Brain (2011)

Effect of no re-exposure on the stability of spatial memory. (A) Experimental design. (B) Probe trial at day 4 (VEH, n = 9; ANI, n = 9). *P < 0.05, time spent in the TQ vs. time spent in the other quadrants by post hoc Newman-Keuls test after significant one-way ANOVA. Error bars are SEM. Time spent (s) in target (T), adjacent left (L), adjacent right (R), and opposite (O) quadrants during the probe trial is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045328&req=5

Figure 3: Effect of no re-exposure on the stability of spatial memory. (A) Experimental design. (B) Probe trial at day 4 (VEH, n = 9; ANI, n = 9). *P < 0.05, time spent in the TQ vs. time spent in the other quadrants by post hoc Newman-Keuls test after significant one-way ANOVA. Error bars are SEM. Time spent (s) in target (T), adjacent left (L), adjacent right (R), and opposite (O) quadrants during the probe trial is shown.
Mentions: As a control experiment, we examined whether the disruption of spatial memory by protein synthesis inhibition depends on memory reactivation at Re-exposure (PT 1). We performed a similar experiment as in Figure 2, except that mice were not given PT 1 (No Re-exposure). However, mice were micro-infused with ANI or VEH into the dorsal hippocampus at 24 h after training on day 2. Both groups of mice showed comparable memory performance and a progressive loss of escape latencies during training (days 1 and 2) (data not shown). In contrast to the results shown in Figure 2, VEH- and ANI-infused mice searched selectively in the TQ in the probe test (VEH, F3,32 = 16.485, P < 0.05; ANI, F3,32 = 10.108, P < 0.05) (Figure 3). ANI-infused mice showed comparable searching scores in the TQ as the VEH group (F1,16 = 0.002, P > 0.05). These results indicated that the inhibition of protein synthesis failed to disrupt spatial memory when the memory was not reactivated by the Re-exposure session, suggesting that the amnesic effects of ANI are contingent on the reactivation of spatial memory.

Bottom Line: We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory.Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription.We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.

ABSTRACT

Background: Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory.

Results: We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1) and L-type voltage gated calcium channels (LVGCCs) in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis.

Conclusions: Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

Show MeSH
Related in: MedlinePlus