Abstract

The calcium-calmodulin–dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)–dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the αCaMKII gene that blocked the autophosphorylation of threonine at position 286 (Thr 286 ) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N -methyl- d -aspartate receptor–dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of αCaMKII at Thr 286 appears to be required for LTP and learning.