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

Cortical plasticity seems to be critical for the establishment of permanent memory traces(1-3). Little is known, however, about the molecular and cellular processes that support consolidation of memories in cortical networks(4,5). Here we show that mice heterozygous for a null mutation of a-calcium-calmodulin kinase II (alpha -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 alpha -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 alpha -CaMKII may modulate the synaptic events required for the consolidation of memory traces in cortical networks.