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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

Chronic calpain inhibition impairs spatial working memory formation in the RAM. Animals in both groups acquired the task (A) with both groups showing pre-surgery latencies that were not significantly different overall or on block 7 or block 8. Post-surgery, there were no differences between Veh and Cal-I groups for within phase errors (B); but a significant increase in across-phase errors for the Cal-I group was seen (C) compared to Veh controls. * p < 0.05.
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brainsci-05-00241-f004: Chronic calpain inhibition impairs spatial working memory formation in the RAM. Animals in both groups acquired the task (A) with both groups showing pre-surgery latencies that were not significantly different overall or on block 7 or block 8. Post-surgery, there were no differences between Veh and Cal-I groups for within phase errors (B); but a significant increase in across-phase errors for the Cal-I group was seen (C) compared to Veh controls. * p < 0.05.

Mentions: In a separate experiment, additional animals were first trained to baseline performance, then surgically implanted with osmotic pumps and catheters which delivered chronic intracerebroventricular (icv) injections of either vehicle (Veh) or calpain inhibitors (Cal-I). Regarding pre-surgical acquisition training, for time to complete the task, a 2 (group) × 8 (training block) repeated measures ANOVA revealed a significant main effect for training block F(7,126) = 20.84, p = 0.001. This indicates that prior to osmotic mini-pump implantation, animals in both the Cal-I group and the Veh group acquired the SWSh task (Figure 4A). There was no main effect for group F(1,18) = 1.203, p = 0.248 and no interaction effect F(7,126) = 1.316, p = 0.248. Visual inspection of Figure 4A suggested a possible difference between our groups on Block 8 of acquisition training and this was tested using an independent samples t-test. The results revealed no significant difference between the groups T(18) = 1.508, p = 0.149 and since the Cal-I group was outperforming the Veh group, the study proceeded. Similar to the data for time to complete the task, a 2 (group) × 8 (training block) repeated measures ANOVA for within-phase errors revealed a significant main effect for training block F(7,126) = 2.92, p = 0.007, a marginal effect for group F(1,18) = 3.397, p = 0.082, and no interaction effect F(7,126) = 1.438, p = 0.196. For across-phase errors there was once again a main effect for training block F(7,126) = 3.072, p = 0.005, no main effect for group F(1,18) = 0.549, p = 0.468, and no interaction effect F(7,126) = 1.765, p = 0.10. Importantly, there was no significant difference between the Cal-I and Veh group on Block 8 for either across-phase errors T(18) = 1.454, p = 0.162 or within-phase errors T(18) = −0.599, p = 0.557.


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)

Chronic calpain inhibition impairs spatial working memory formation in the RAM. Animals in both groups acquired the task (A) with both groups showing pre-surgery latencies that were not significantly different overall or on block 7 or block 8. Post-surgery, there were no differences between Veh and Cal-I groups for within phase errors (B); but a significant increase in across-phase errors for the Cal-I group was seen (C) compared to Veh controls. * p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

brainsci-05-00241-f004: Chronic calpain inhibition impairs spatial working memory formation in the RAM. Animals in both groups acquired the task (A) with both groups showing pre-surgery latencies that were not significantly different overall or on block 7 or block 8. Post-surgery, there were no differences between Veh and Cal-I groups for within phase errors (B); but a significant increase in across-phase errors for the Cal-I group was seen (C) compared to Veh controls. * p < 0.05.
Mentions: In a separate experiment, additional animals were first trained to baseline performance, then surgically implanted with osmotic pumps and catheters which delivered chronic intracerebroventricular (icv) injections of either vehicle (Veh) or calpain inhibitors (Cal-I). Regarding pre-surgical acquisition training, for time to complete the task, a 2 (group) × 8 (training block) repeated measures ANOVA revealed a significant main effect for training block F(7,126) = 20.84, p = 0.001. This indicates that prior to osmotic mini-pump implantation, animals in both the Cal-I group and the Veh group acquired the SWSh task (Figure 4A). There was no main effect for group F(1,18) = 1.203, p = 0.248 and no interaction effect F(7,126) = 1.316, p = 0.248. Visual inspection of Figure 4A suggested a possible difference between our groups on Block 8 of acquisition training and this was tested using an independent samples t-test. The results revealed no significant difference between the groups T(18) = 1.508, p = 0.149 and since the Cal-I group was outperforming the Veh group, the study proceeded. Similar to the data for time to complete the task, a 2 (group) × 8 (training block) repeated measures ANOVA for within-phase errors revealed a significant main effect for training block F(7,126) = 2.92, p = 0.007, a marginal effect for group F(1,18) = 3.397, p = 0.082, and no interaction effect F(7,126) = 1.438, p = 0.196. For across-phase errors there was once again a main effect for training block F(7,126) = 3.072, p = 0.005, no main effect for group F(1,18) = 0.549, p = 0.468, and no interaction effect F(7,126) = 1.765, p = 0.10. Importantly, there was no significant difference between the Cal-I and Veh group on Block 8 for either across-phase errors T(18) = 1.454, p = 0.162 or within-phase errors T(18) = −0.599, p = 0.557.

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