Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory.
Cortical plasticity seems to be critical for the establishment of permanent memory traces. Little is known, however, about the molecular and cellular processes that support consolidation of memories in cortical networks. Here we show that mice heterozygous for a null mutation of alpha-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.
Frankland
P W
PW
Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California 90095-1761, USA.
O'Brien
C
C
Ohno
M
M
Kirkwood
A
A
Silva
A J
AJ
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D004594:Electrophysiology; D004597:Electroshock; D005239:Fear / Q000502:physiology; D017353:Gene Deletion; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse