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Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long-Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing Valences

View Article: PubMed Central - PubMed

ABSTRACT

NF-kappa B is a transcription factor whose activation has been shown to be necessary for long-term memory consolidation in several species. NF-kappa B is activated and translocates to the nucleus of cells in a specific temporal window during consolidation. Our work focuses on a one trial learning tasks associated to the inhibitory avoidance (IA) setting. Mice were trained either receiving or not a footshock when entering a dark compartment (aversive vs. appetitive learning). Regardless of training condition (appetitive or aversive), latencies to step-through during testing were significantly different to those measured during training. Additionally, these testing latencies were also different from those of a control group that only received a shock unrelated to context. Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive and the appetitive tasks when compared with control and naïve animals. NF-kappa B inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or Nucleus accumbens immediately after training was able to impair retention in both training versions. Our results suggest that NF-kappa B is a critical molecular step, in different brain areas on memory consolidation. This was the case for both the IA task and also the modified version of the same task where the footshock was omitted during training. This work aims to further investigate how appetitive and aversive memories are consolidated.

No MeSH data available.


Related in: MedlinePlus

Intra-hippocampal injections of sulfasalazine impair aversive and appetitive memory. (A) Mouse atlas sections corresponding to the targeted distance from Bregma are shown. Gray represents the maximum area reached by India ink. Asterisks indicate tip of infusion cannula. (B) Latencies to step-through during training for animals in the S, and U groups prior to injection with either Sulfasalazine (Sulfa) or Vehicle (Veh). (C) Latencies to step-through during testing 48 h post-training for S, Si and U groups injected with either Sulfa or Veh immediately post-training. Bars show medians with interquartile ranges. *P < 0.01.
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Figure 3: Intra-hippocampal injections of sulfasalazine impair aversive and appetitive memory. (A) Mouse atlas sections corresponding to the targeted distance from Bregma are shown. Gray represents the maximum area reached by India ink. Asterisks indicate tip of infusion cannula. (B) Latencies to step-through during training for animals in the S, and U groups prior to injection with either Sulfasalazine (Sulfa) or Vehicle (Veh). (C) Latencies to step-through during testing 48 h post-training for S, Si and U groups injected with either Sulfa or Veh immediately post-training. Bars show medians with interquartile ranges. *P < 0.01.

Mentions: To compare the role of the NF-kappa B pathway in the hippocampus, these types of learning animals were injected with the NF-kappa B pathway inhibitor Sulfasalazine. Immediately after training either 1 μg/hippocampus Sulfasalazine in DMSO solution or DMSO (vehicle) was injected (Figure 3A). The groups of animals showed no differences in their step-through latencies during training, before the injection of either drug or vehicle (Figure 3B). When comparing only vehicle injected animals, the same pattern evidenced in Figure 1A is observed, S Veh animals show higher latencies to step-through than Si Veh animals (Mann-Whitney U = 0.0; p < 0.01; Median S Veh = 300, n = 7; Median Si Veh = 15, n = 7); while U Veh animals show lower latencies to step-though when compared to Si animals (Mann-Whitney U = 1.0; p < 0.01, Median Si Veh = 15, n = 7; Median U Veh = 4, n = 7), evidencing retention in both S Veh and U Veh groups (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). Si animals injected with Sulfasalazine (Si Sulfa) show no significant differences in latencies to step-through during testing when compared to Si animals injected with vehicle (Si Veh; Mann-Whitney U = 22.5; p = 0.845, Median Si Veh = 15, n = 7; Median Si Sulfa = 15, n = 7) (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). As described previously in our lab (Boccia et al., 2007), S animals injected with sulfasalazine (S Sulfa) showed lower latencies to step-through than S animals injected with vehicle (S Veh; Mann-Whitney U = 0.0; p < 0.01; Median S Veh = 300, n = 7; Median S Sulfa = 78, n = 7); showing that Sulfasalazine injected post-training intra-hippocampus impairs memory consolidation for S animals (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). Interestingly, U animals injected with sulfasalazine (U Sulfa) showed higher latencies to step-through than U animals injected with vehicle (U Veh; Mann-Whitney U = 0.5; p < 0.01; Median U Veh = 4, n = 7; Median U Sulfa = 13, n = 7); indicating that Sulfasalazine is causing memory impairment in the U group of animals as well as the S group of animals (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). This experiment shows that both S and U animals form hippocampal dependent memories that can be impaired when injecting an inhibitor of the NF-kappa B pathway such as Sulfasalazine. Therefore the NF-kappa B pathway in the hippocampus is necessary for the consolidation of contextual-associative memories both for S and U tasks.


Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long-Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing Valences
Intra-hippocampal injections of sulfasalazine impair aversive and appetitive memory. (A) Mouse atlas sections corresponding to the targeted distance from Bregma are shown. Gray represents the maximum area reached by India ink. Asterisks indicate tip of infusion cannula. (B) Latencies to step-through during training for animals in the S, and U groups prior to injection with either Sulfasalazine (Sulfa) or Vehicle (Veh). (C) Latencies to step-through during testing 48 h post-training for S, Si and U groups injected with either Sulfa or Veh immediately post-training. Bars show medians with interquartile ranges. *P < 0.01.
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Figure 3: Intra-hippocampal injections of sulfasalazine impair aversive and appetitive memory. (A) Mouse atlas sections corresponding to the targeted distance from Bregma are shown. Gray represents the maximum area reached by India ink. Asterisks indicate tip of infusion cannula. (B) Latencies to step-through during training for animals in the S, and U groups prior to injection with either Sulfasalazine (Sulfa) or Vehicle (Veh). (C) Latencies to step-through during testing 48 h post-training for S, Si and U groups injected with either Sulfa or Veh immediately post-training. Bars show medians with interquartile ranges. *P < 0.01.
Mentions: To compare the role of the NF-kappa B pathway in the hippocampus, these types of learning animals were injected with the NF-kappa B pathway inhibitor Sulfasalazine. Immediately after training either 1 μg/hippocampus Sulfasalazine in DMSO solution or DMSO (vehicle) was injected (Figure 3A). The groups of animals showed no differences in their step-through latencies during training, before the injection of either drug or vehicle (Figure 3B). When comparing only vehicle injected animals, the same pattern evidenced in Figure 1A is observed, S Veh animals show higher latencies to step-through than Si Veh animals (Mann-Whitney U = 0.0; p < 0.01; Median S Veh = 300, n = 7; Median Si Veh = 15, n = 7); while U Veh animals show lower latencies to step-though when compared to Si animals (Mann-Whitney U = 1.0; p < 0.01, Median Si Veh = 15, n = 7; Median U Veh = 4, n = 7), evidencing retention in both S Veh and U Veh groups (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). Si animals injected with Sulfasalazine (Si Sulfa) show no significant differences in latencies to step-through during testing when compared to Si animals injected with vehicle (Si Veh; Mann-Whitney U = 22.5; p = 0.845, Median Si Veh = 15, n = 7; Median Si Sulfa = 15, n = 7) (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). As described previously in our lab (Boccia et al., 2007), S animals injected with sulfasalazine (S Sulfa) showed lower latencies to step-through than S animals injected with vehicle (S Veh; Mann-Whitney U = 0.0; p < 0.01; Median S Veh = 300, n = 7; Median S Sulfa = 78, n = 7); showing that Sulfasalazine injected post-training intra-hippocampus impairs memory consolidation for S animals (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). Interestingly, U animals injected with sulfasalazine (U Sulfa) showed higher latencies to step-through than U animals injected with vehicle (U Veh; Mann-Whitney U = 0.5; p < 0.01; Median U Veh = 4, n = 7; Median U Sulfa = 13, n = 7); indicating that Sulfasalazine is causing memory impairment in the U group of animals as well as the S group of animals (Kruskal-Wallis statistic H(5,36) = 35.41, p < 0.01; Figure 3C). This experiment shows that both S and U animals form hippocampal dependent memories that can be impaired when injecting an inhibitor of the NF-kappa B pathway such as Sulfasalazine. Therefore the NF-kappa B pathway in the hippocampus is necessary for the consolidation of contextual-associative memories both for S and U tasks.

View Article: PubMed Central - PubMed

ABSTRACT

NF-kappa B is a transcription factor whose activation has been shown to be necessary for long-term memory consolidation in several species. NF-kappa B is activated and translocates to the nucleus of cells in a specific temporal window during consolidation. Our work focuses on a one trial learning tasks associated to the inhibitory avoidance (IA) setting. Mice were trained either receiving or not a footshock when entering a dark compartment (aversive vs. appetitive learning). Regardless of training condition (appetitive or aversive), latencies to step-through during testing were significantly different to those measured during training. Additionally, these testing latencies were also different from those of a control group that only received a shock unrelated to context. Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive and the appetitive tasks when compared with control and na&iuml;ve animals. NF-kappa B inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or Nucleus accumbens immediately after training was able to impair retention in both training versions. Our results suggest that NF-kappa B is a critical molecular step, in different brain areas on memory consolidation. This was the case for both the IA task and also the modified version of the same task where the footshock was omitted during training. This work aims to further investigate how appetitive and aversive memories are consolidated.

No MeSH data available.


Related in: MedlinePlus