Spatial Distribution Patterns of Alpha-CaMKII in Hippocampal Tissue Suggest Role for Transient Not Persistent Translocation in Chemical LTP and Persistent Clustering in Ischemia

Calcium.calmodulin-dependent protein kinase II (alpha-CaMKII) forms punctate structures in dendritic spines and in the soma of hippocampal pyramidal neurons upon calcium elevation evoked by N-methyl-D-aspartic acid receptor (NMDAR) stimulation. Though advocated to be relevant to memory formation, it is not clear whether spinal accumulation represents translocation to and interaction with NMDAR or, as somal punctate accumulation, it is the result of self-association representing clustering of alpha-CaMKII. Alpha-CaMKII punctate accumulation can be transient or persistent, the significance of temporal pattern to memory formation and excito-toxicity is however not clear either. In order to obtain a clearer understanding of the state of alpha-CaMKII in memory formation and excito-toxic insult, e.g. ischemia, we carried out an extensive ultrastructural study of alpha-CaMKII distribution in control, in chemically induced long-term potentiation (cLTP) and ischemic conditions in rat CA1 hippocampal slices by electron microscopy and immunogold labeling. We found preferential localization of alpha-CaMKII to post-synaptic densities in all three conditions but no significant differences between the distributions of alpha-CaMKII, phospho-Thr286-alpha-CaMKII and phospho-Thr305-alpha-CaMKII when comparing control and cLTP treated slices. The number of alpha-CaMKII clusters was significantly greater in the ischemic than in the control and cLTP treated slices. Thus, contrary to expectations, we found no evidence of significant persistent alpha-CaMKII accumulation in the dendritic spines in cLTP and conclude that transient rather than persistent translocation of alpha-CaMKII to the post-synaptic membrane is relevant to LTP induction. This is consistent with a switch-like rather than a resident role for alpha-CaMKII in memory formation. Our data further show that cluster formation is a hallmark of ischemic insult and not relevant to memory formation.