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α-CaMKII-dependent plasticity in the cortex is required for permanent memory

Abstract

Cortical plasticity seems to be critical for the establishment of permanent memory traces1,2,3. Little is known, however, about the molecular and cellular processes that support consolidation of memories in cortical networks4,5. Here we show that mice heterozygous for a null mutation of α-calcium-calmodulin kinase II (α-CaMKII+/-) show normal learning and memory 1–3 days after training in two hippocampus-dependent tasks. However, their memory is severely impaired at longer retention delays (10–50 days). Consistent with this, we found that α-CaMKII+/- mice have impaired cortical, but not hippocampal, long-term potentiation. Our results represent a first step in unveiling the molecular and cellular mechanisms underlying the establishment of permanent memories, and they indicate that α-CaMKII may modulate the synaptic events required for the consolidation of memory traces in cortical networks.

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Figure 1: Contextual memory in α-CaMKII+/- mutants.
Figure 2: Spatial memory in α-CaMKII+/- mutants.
Figure 3: Reduced cortical LTP in α-CaMKII+/- mutants.

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Acknowledgements

We thank S. Anagnostaras, R. Costa, S. Josselyn, S. Köhler, S. Kushner, G. Murphy and K. Nader for comments on the paper. These studies were supported by grants from NIH, National Eye Institute (A.K.), FRAXA Research Foundation (P.W.F.), and the Whitehall, Beckman, Merck, Klingenstein and McKnight Foundations (A.J.S.).

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Correspondence to Alcino J. Silva.

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Frankland, P., O'Brien, C., Ohno, M. et al. α-CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature 411, 309–313 (2001). https://doi.org/10.1038/35077089

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