Behavioural memory reconsolidation of food and fear memories - PubMed (original) (raw)

Behavioural memory reconsolidation of food and fear memories

Charlotte R Flavell et al. Nat Commun. 2011.

Abstract

The reactivation of a memory through retrieval can render it subject to disruption or modification through the process of memory reconsolidation. In both humans and rodents, briefly reactivating a fear memory results in effective erasure by subsequent extinction training. Here we show that a similar strategy is equally effective in the disruption of appetitive pavlovian cue-food memories. However, systemic administration of the NMDA receptor partial agonist D-cycloserine, under the same behavioural conditions, did not potentiate appetitive memory extinction, suggesting that reactivation does not enhance subsequent extinction learning. To confirm that reactivation followed by extinction reflects a behavioural analogue of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the L-type voltage-gated calcium channel blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories.

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Figures

Fig. 1

Fig. 1

Acquisition of a new response with conditioned reinforcement. Discriminated responding on the active (open symbols) and inactive (filled symbols) levers was compared across experimental conditions. a, Extinction (E) alone, without prior memory reactivation (N=7). b, reactivation (R) followed, 1 hr later, by extinction (N=7). c, reactivation followed, 6 hr later, by extinction (N=8). d, context exposure (CX) followed, 1 hr later, by extinction (N=12). e, exposure to modified (mod) context followed, 1 hr later, by extinction (N=7). f, pretraining context habituation (pre-ex), with posttraining context exposure followed, 1 hr later, by extinction (N=7). Groups b, d & e differed significantly from the control group a. Groups c & f did not differ from group a. Data presented as mean ± SEM.

Fig. 2

Fig. 2

No differences between groups prior to acquisition of a new response with conditioned reinforcement. The groups were extinction alone (E; N=7), reactivation + extinction with a 1-hr interval (1-hr; N=7), reactivation + extinction with a 6-hr interval (6-hr, N=8), context exposure followed by extinction (CX; N=12), exposure to modified context prior to extinction (mod; N=7) and pre-exposure to the context before training (pre-ex; N=7). a, Total number of CS–sucrose pairings during training across all groups. b, Number of unreinforced CS presentations during memory reactivation in groups 1-hr and 6-hr compared to the equivalent first 10 min of extinction in group E. c, Number of unreinforced CS presentations during memory extinction across all groups compared to the equivalent final 60 min of extinction in group E. Data presented as mean + SEM.

Fig. 3

Fig. 3

D-cycloserine potentiates extinction when the extinction session is 3 hr but not 1 hr long. Discriminated responding on the active (open symbols) and inactive (filled symbols) levers was compared across experimental conditions. a, Saline injection prior to 1 hr extinction (N=7). b, DCS injection prior to 1 hr extinction (N=8). c, Saline injection prior to 3 hr extinction (N=7). d, DCS injection prior to 1 hr extinction (N=8). DCS had no effect upon the acquisition of discriminated responding with conditioned reinforcement with the 1-hr extinction session, but did retard acquisition with the 3-hr session. Data presented as mean ± SEM.

Fig. 4

Fig. 4

Fear conditioning to a discrete clicker. Rats were reactivated and extinguished 1 hr later (filled columns/symbols, N=8) or given extinction alone (open columns/symbols, N=8). a, Freezing to the clicker at reactivation/start of extinction (R/E) and at the post-extinction test. Reactivation and extinction impaired the decrement in memory expression compared to extinction alone. b, Freezing during the extinction session. The final 10 presentations of the CS (i.e. excluding the initial presentation of extinction or the prior reactivation presentation) are presented. The reduction in freezing levels across CS presentations was retarded in the reactivation + extinction condition, compared to the extinction alone condition (mixed ANOVA; presentation × condition: F(4.6,64.3)=3.025, p=0.019; condition: F(1,14)=1.228, p=0.286). Analysis of simple effects (p<0.05) revealed that both conditions reduced their freezing levels across the session, and there was no absolute difference between the conditions at any of the CS presentations. Data presented as mean ± SEM.

Fig. 5

Fig. 5

Post-reactivation Nimodipine prevents behavioural memory updating. a, Experimental timeline. Following contextual fear conditioning (C), Nimodipine was injected immediately after memory reactivation (R), and hence 1 hr before extinction (E). b, Subsequent freezing behaviour was compared across the post-reactivation/extinction test (T1/Test 1) and the post-reacquisition test (T2/Test 2). Nimodipine-treated rats (filled columns/symbols) readily reconditioned, whereas vehicle-treated (open columns/symbols) rats showed a persistent impairment in contextual fear. c, Freezing during the extinction session itself did not differ between groups. Contextual freezing was compared across seven 4-min bins corresponding to the final 28 min of extinction after reactivation or the first 2 min of extinction. There were no differences between the groups during extinction (bin × treatment: F(2.0,20.5)=0.321, p=0.733; treatment: F(1,10)=0.374, p=0.554). While there was a trend for both groups to reduce their freezing response to the context over the course of the session, this was not statistically significant (bin: F(2.0,20.5)=5.743, p=0.066). Data presented as mean + SEM. N=6 per group.

Fig. 6

Fig. 6

Pre-extinction Nimodipine has no effect upon memory extinction. a, Experimental timeline. Following contextual fear conditioning (C), Nimodipine was injected 1 hr before extinction (E). b, Subsequent freezing behaviour was compared across the post-reactivation/extinction test (T1/Test 1) and the post-reacquisition test (T2/Test 2). Both vehicle- (open columns/symbols) and Nimodipine-treated (filled columns/symbols) rats readily reconditioned. c, Freezing during the extinction session itself did not differ between groups. Contextual freezing was compared across seven 4-min bins corresponding to the final 28 min of extinction after reactivation or the first 2 min of extinction. There were no differences between the groups during extinction (bin × treatment: F(2.2,22.1)=2.038, p=0.150; treatment: F(1,10)=0.020, p=0.889). However, there was also no evidence for a reduction of freezing over the course of the session (bin: F(2.2,22.1)=1.762, p=0.193). Data presented as mean + SEM. N=6 per group.

Fig. 7

Fig. 7

Post-extinction Nimodipine has no effect upon behavioural memory updating. a, Experimental timeline. Following contextual fear conditioning (C) and memory reactivation (R), Nimodipine was injected immediately after extinction (E). b, Subsequent freezing behaviour was compared across the post-reactivation/extinction test (T1/Test 1) and the post-reacquisition test (T2/Test 2). Both vehicle- (open columns/symbols) and Nimodipine-treated (filled columns/symbols) rats readily reconditioned. c, Freezing during the extinction session itself did not differ between groups. Contextual freezing was compared across seven 4-min bins corresponding to the final 28 min of extinction after reactivation or the first 2 min of extinction. There were no differences between the groups during extinction (bin × treatment: F(1.6,15.8)=0.858, p=0.418; treatment: F(1,10)=0.342, p=0.572). Both groups extinguished their freezing response to the context over the course of the session (bin: F(1.6,15.8)=5.743, p=0.018). Data presented as mean + SEM. N=6 per group.

Fig. 8

Fig. 8

Post-extinction Nimodipine impairs memory extinction. a, Experimental timeline. Following contextual fear conditioning (C), Nimodipine was injected after extinction (E). b, Subsequent freezing behaviour was compared across the post-reactivation/extinction test (T1/Test 1) and the post-reacquisition test (T2/Test 2). Nimodipine-treated rats (filled columns/symbols) were impaired compared to vehicle-treated controls (open columns/symbols) in extinction retention at Test 1. c, Freezing during the extinction session itself did not differ between groups. Contextual freezing was compared across seven 4-min bins corresponding to the final 28 min of extinction after reactivation or the first 2 min of extinction. There were no differences between the groups during extinction (bin × treatment: F(2.4,24.1)=1.421, p=0.262; treatment: F(1,10)=1.608, p=0.234). Both groups showed extinguished their freezing response to the context over the course of the session (bin: F(2.4,24.1)=5.078, p=0.011) Data presented as mean + SEM. N=6 per group.

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