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αCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory

Nature Neuroscience volume 8, pages 411–412 (2005)Cite this article

Abstract

Autophosphorylation of α calcium–calmodulin-dependent kinase II (αCaMKII) has been proposed to be the key event in memory storage. We tested this hypothesis with autophosphorylation-deficient mutant mice in hippocampus- and amygdala-dependent learning and memory tasks and found that the autophosphorylation of αCaMKII was required for rapid learning but was not essential for memory. We conclude that αCaMKII autophosphorylation contributes to single-trial learning but is dispensable for memory.

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Figure 1: In the passive avoidance task, the αCaMKII-T286A mutant mice have retarded learning but normal memory.
Figure 2: Learning but not memory is affected in both contextual and cued fear conditioning in the αCaMKII-T286A mutants.

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Acknowledgements

We thank T.V.P. Bliss, S.P.R. Rose and C.H. Yeo for critical reading of the manuscript. This work was funded by the Biotechnology and Biological Sciences Research Council Neurone Initiative and a Medical Research Council Career Establishment Grant.

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  1. Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Elaine E Irvine, Jeffrey Vernon & K Peter Giese

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  1. Elaine E Irvine
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  2. Jeffrey Vernon
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  3. K Peter Giese
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Correspondence to K Peter Giese.

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Supplementary information

Supplementary Fig. 1

The αCaMKII-T286A mutant mice have impaired immediate avoidance. Data represent step-through latencies (mean ± s.e.m.) during multiple trial avoidance training. The latency to enter the dark compartment on the second trial was significantly longer only for the wild-type mice. Two-way repeated measures ANOVA revealed a time x genotype interaction F1,29 = 119.2, P ⩽ 0.001; *** P ⩽ 0.001 compared to training latency. (PDF 959 kb)

Supplementary Fig. 2

Training with three tone-shock pairings results in cued but not contextual fear memory in the αCaMKII-T286A mutant mice. Data represent percentage freezing (mean ± s.e.m.). (a) Mice were conditioned with a three tone-shock protocol (WT, n = 11, and T286A, n = 10). (b) 24 hours later the mutants were impaired in contextual fear conditioning (U = 10.5; WT, n = 11; T286A, n = 10; two-tailed P ⩽ 0.001); *** P ⩽ 0.001 (c) When tested 48 hours after conditioning both genotypes froze significantly more during tone presentation. Two-way repeated measures ANOVA showed an effect of training F1,19 = 86.9, P ⩽0.001, but no effect of genotype F1,19 = 2.7 or interaction F1,19 = 0.7; *** P ⩽ 0.001 compared to pre-CS freezing. (PDF 1235 kb)

Supplementary Fig. 3

Cued fear memory is stable in the αCaMKII-T286A mutant mice. Data represent percentage freezing (mean ± s.e.m.). Thirty days after the initial test both genotypes froze significantly more during tone presentation. Two-way repeated measures ANOVA revealed an effect of tone F1,16 = 48.0, P ⩽ 0.001, but no effect of genotype F1,16 = 1.0 or interaction F1,16 = 0.1; *** P ⩽ 0.001 compared to pre-CS freezing. (PDF 974 kb)

Supplementary Methods (PDF 33 kb)

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Irvine, E., Vernon, J. & Giese, K. αCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory. Nat Neurosci 8, 411–412 (2005). https://doi.org/10.1038/nn1431

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