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), 116-25. (doi:10.1101/lm.023937.111). (PMID:22366775).
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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.
|Digital Object Identifier (DOI):||doi:10.1101/lm.023937.111|
|Subjects:||Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences > Molecular & Cellular
|Date Deposited:||20 Apr 2012 08:40|
|Last Modified:||06 Aug 2015 03:05|
A Systems Biological Approach to Elucidate Local Protein Synthesis Code in Plasticity and Memory
Funded by: BBSRC (BB/I004483/1)
Led by: Chris Proud
1 November 2010 to 31 August 2013
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