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Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice

Gildish, Iness, Manor, David, David, Orit, Sharma, Vijendra, Williams, David, Agarwala, Usha, Wang, Xuemin, Kenney, Justin W, Proud, Chris G and Rosenblum, Kobi (2012) Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice Learning & Memory, 19, (3), pp. 116-25. (doi:10.1101/lm.023937.111). (PMID:22366775).

Record type: Article

Abstract

Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment.

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e-pub ahead of print date: February 2012
Published date: March 2012
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 337175
URI: http://eprints.soton.ac.uk/id/eprint/337175
ISSN: 1072-0502
PURE UUID: 6e2c9ae2-e00e-40fc-a57b-0ca0f12ae383

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Date deposited: 20 Apr 2012 08:40
Last modified: 18 Jul 2017 06:04

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Contributors

Author: Iness Gildish
Author: David Manor
Author: Orit David
Author: Vijendra Sharma
Author: David Williams
Author: Usha Agarwala
Author: Xuemin Wang
Author: Justin W Kenney
Author: Chris G Proud
Author: Kobi Rosenblum

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