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Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

Olson ML, Ingebretson AE, Harmelink KM - Brain Sci (2015)

Bottom Line: Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression.Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training.These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology and Program in Neuroscience, Concordia College, Moorhead, MN 56562, USA. molson@cord.edu.

ABSTRACT
The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

No MeSH data available.


Related in: MedlinePlus

Mean latencies to complete the training phase of the SWSh RAM task during acquisition. Each data point represents the group mean (±SEM) of each experimental group for training block 1–8.
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brainsci-05-00241-f001: Mean latencies to complete the training phase of the SWSh RAM task during acquisition. Each data point represents the group mean (±SEM) of each experimental group for training block 1–8.

Mentions: Figure 1 depicts mean latencies to complete the training phase of the SWSh task during task acquisition. Data for each rat’s daily task performance were averaged across two to three-day blocks in order to account for the fact that there were differences in the number of acquisition days required to reach baseline performance (21–24 days). The result of this was that each rat had a score for block 1–8 of acquisition training. The data points in Figure 1 represent group averages for each of these blocks. For latency to complete the task, a 3 (group) × 8 (training block) repeated measures ANOVA was conducted and revealed a significant main effect for training block: F(7,154) = 7.426, p = 0.000, no main effect for group F(2,22) = 2.395, p = 0.12, and no interaction effect F(14,154) = 1.026, p = 0.454. The significant effect for training block indicates that animals in all groups learned the task during the acquisition period. Similarly, for within-phase errors, there was a significant effect for training block F (7,154) = 3.044, p = 0.031, no significant effect for group F(2,22) = 2.353, p = 0.12, and no significant interaction effect F(14,154) = 0.918, p = 0.54. For across-phase errors, there was no significant effect for training block F (7,154) = 1.759, p = 0.1, a significant effect for group F (2,22) = 3.956, p = 0.034, and no significant interaction effect F (14,154) = 0.514, p = 0.922. The significant group effect for across-phase errors was found between the 30 min and 4 h groups (Tukey’s = p = 0.039), but not the 5 min group, indicating that the 4 h group took longer than the 30 min group to acquire the task with regard to across-phase errors. Importantly, one-way ANOVAs showed that there were no differences between any of the groups on block 7 or block 8, indicating that there were no group differences in across-phase errors by the end of the acquisition phase.


Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

Olson ML, Ingebretson AE, Harmelink KM - Brain Sci (2015)

Mean latencies to complete the training phase of the SWSh RAM task during acquisition. Each data point represents the group mean (±SEM) of each experimental group for training block 1–8.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493467&req=5

brainsci-05-00241-f001: Mean latencies to complete the training phase of the SWSh RAM task during acquisition. Each data point represents the group mean (±SEM) of each experimental group for training block 1–8.
Mentions: Figure 1 depicts mean latencies to complete the training phase of the SWSh task during task acquisition. Data for each rat’s daily task performance were averaged across two to three-day blocks in order to account for the fact that there were differences in the number of acquisition days required to reach baseline performance (21–24 days). The result of this was that each rat had a score for block 1–8 of acquisition training. The data points in Figure 1 represent group averages for each of these blocks. For latency to complete the task, a 3 (group) × 8 (training block) repeated measures ANOVA was conducted and revealed a significant main effect for training block: F(7,154) = 7.426, p = 0.000, no main effect for group F(2,22) = 2.395, p = 0.12, and no interaction effect F(14,154) = 1.026, p = 0.454. The significant effect for training block indicates that animals in all groups learned the task during the acquisition period. Similarly, for within-phase errors, there was a significant effect for training block F (7,154) = 3.044, p = 0.031, no significant effect for group F(2,22) = 2.353, p = 0.12, and no significant interaction effect F(14,154) = 0.918, p = 0.54. For across-phase errors, there was no significant effect for training block F (7,154) = 1.759, p = 0.1, a significant effect for group F (2,22) = 3.956, p = 0.034, and no significant interaction effect F (14,154) = 0.514, p = 0.922. The significant group effect for across-phase errors was found between the 30 min and 4 h groups (Tukey’s = p = 0.039), but not the 5 min group, indicating that the 4 h group took longer than the 30 min group to acquire the task with regard to across-phase errors. Importantly, one-way ANOVAs showed that there were no differences between any of the groups on block 7 or block 8, indicating that there were no group differences in across-phase errors by the end of the acquisition phase.

Bottom Line: Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression.Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training.These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology and Program in Neuroscience, Concordia College, Moorhead, MN 56562, USA. molson@cord.edu.

ABSTRACT
The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

No MeSH data available.


Related in: MedlinePlus