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

Mikel Olson,Katherine Harmelink,Anna Ingebretson

doi:10.3390/brainsci5020241

Mikel Olson, Katherine Harmelink + Show 1 more

Open Access

https://doi.org/10.3390/brainsci5020241

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Journal: Brain sciences	Publication Date: Jun 19, 2015
Citations: 40	License type: CC BY 4.0

Affiliation: Concordia College - Minnesota

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.

Highlights

A functioning hippocampus is essential for optimal declarative memory formation
Our main finding from the first experiment is that both total cortactin and Y421- phosphorylated cortactin are reduced 30 min post-training in the radial arm maze (RAM)
The magnitude of the reduction in total cortactin we observed is consistent with a previous report which demonstrated reduced hippocampal cortactin levels following spatial memory training in the water maze [19]

Summary

Introduction

A functioning hippocampus is essential for optimal declarative memory formation. Declarative memories that include information about the spatial environment or an organism’s orientation to thatBrain Sci. 2015, 5 environment (spatial memories) are affected by hippocampal dysfunction [1]. Declarative memories that include information about the spatial environment or an organism’s orientation to that. The mechanism by which the hippocampus aids in the consolidation of memories is the subject of a sizeable body of research and many molecules which subserve memory formation in the hippocampus have been identified. Of these molecules, those which regulate the structure of dendritic spines may be especially important for ensuring the ongoing stability of a newly formed memory [4]. Dysregulation of dendritic spine structure has been implicated in many human psychological and neurological disorders that include symptomatic declarative memory impairments [5]. Among the factors that are believed to drive dendritic structural changes in healthy neurons are glutamate signaling and subsequent activation of N-Methyl-D-Aspartate (NMDA) receptors, events which are crucial for hippocampus-dependent memory formation [6,7] and long-term potentiation (LTP) [8,9]

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