The calcium-calmodulin-dependent kinase II (CaMKII) is required for hi
ppocampal longterm potentiation (LTP) and spatial learning. In additio
n to its calcium-calmodulin (CaM)dependent activity, CaMKII can underg
o autophosphorylation, resulting in CaM-independent activity. A point
mutation was introduced into the alpha CaMKII gene that blocked the au
tophosphorylation of threonine at position 286 (Thr(286)) Of this kina
se without affecting its CaM-dependent activity, The mutant mice had n
o N-methyl-D-aspartate receptor-dependent LTP in the hippocampal CAI a
rea and showed no spatial learning in the Morris water maze. Thus, the
autophosphorylation of alpha CaMII at Thr(286) appears to be required
for LTP and learning.