title: An endogenous inhibitor of calcium/calmodulin-dependent kinase II is up-regulated during consolidation of fear memory.
abstract: CaMKIINalpha and CaMKIINbeta are endogenous inhibitors of the abundant synaptic protein, calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII exerts a prominent function in memory formation and the endogenous inhibitors might be important regulators of CaMKII activity during this process. Here we investigated whether or not CaMKIINalpha and CaMKIINbeta gene expressions are regulated in the mouse hippocampus and amygdala after background contextual fear conditioning. Quantitative real-time PCR revealed that the hippocampal expression of CaMKIINalpha mRNA was up-regulated 30 and 60 min after conditioning. In contrast, CaMKIINbeta mRNA expression did not change. The up-regulation of CaMKIINalpha expression was specific for the fear memory because the context alone and a shock control did not induce any variation of transcription level. Quantification of in situ hybridization signals showed that CaMKIINalpha expression increased in hippocampal area CA1, in the dentate gyrus (DG) and in the lateral amygdala (LA) 30 min after training. Our findings show an up-regulation in the expression of the endogenous inhibitor gene CaMKIINalpha during consolidation of fear memory. The early onset and the amplitude of the up-regulation are similar to those of immediate-early genes. Taken together, our results suggest that the CaMKIINalpha inhibitor has a physiological role in controlling CaMKII activity from an early stage of memory consolidation.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Lepicard
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes-Martins
authors.forename: Laura S J
authors.initials: LS
authors.lastname: von Hertzen
authors.forename: K Peter
authors.initials: KP
authors.lastname: Giese
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases