title: Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.
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.
authors.affiliation: Department of Neurobiology, University of Haifa, Haifa 31905, Israel.
authors.forename: Iness
authors.initials: I
authors.lastname: Gildish
authors.forename: David
authors.initials: D
authors.lastname: Manor
authors.forename: Orit
authors.initials: O
authors.lastname: David
authors.forename: Vijendra
authors.initials: V
authors.lastname: Sharma
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Usha
authors.initials: U
authors.lastname: Agarwala
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.forename: Justin W
authors.initials: JW
authors.lastname: Kenney
authors.forename: Chris G
authors.initials: CG
authors.lastname: Proud
authors.forename: Kobi
authors.initials: K
authors.lastname: Rosenblum
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001923:Brain Chemistry / Q000235:genetics* / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D054736:Elongation Factor 2 Kinase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008345:Manganese; D008568:Memory / Q000502:physiology; D051379:Mice; D010766:Phosphorylation / Q000235:genetics; D055697:Taste Perception / Q000235:genetics* / Q000502:physiology
chemical_list: D008345:Manganese; D054736:Elongation Factor 2 Kinase