Plasticity-specific phosphorylation of CaMKII, MAP-kinases and CREB during late-LTP in rat hippocampal slices in vitro

Processes of learning, memory formation and functional plasticity, such as long-term potentiation (LTP) are associated with activity changes of alphaCaMKII, MAPKs and CREB proteins. Little is known on the temporal regulation of the phosphorylation states of these proteins during late-LTP, a period which requires the synthesis of new macromolecules and has been postulated to correlate with the consolidation of a memory trace at the cellular level. We now present data from hippocampal slices in vitro obtained from adult rats that describe such specific phosphorylation changes of the above mentioned three molecules during early- and late-LTP. We detail that LTP induction and its maintenance reveals a delayed onset of continuous CREB phosphorylation with two separate peaks at 45 min and 6 h before it decays back to baseline phosphorylation levels; whereas alphaCaMKII and MAPK2 remain in a specific, but enhanced phosphorylation state throughout the induction, early- and late-LTP. These LTP-regulated phosphorylation events were NMDAR-dependent and upon the activity of a translated serine-threonine kinase. Interestingly, only the late enhancement of pCREB was clearly dependent on protein synthesis. Our data extend results describing the regulation of alphaCaMKII, MAPKs and CREB phosphorylation during early stages of LTP, suggesting a specific role of these enzymes also during phases of LTP consolidation in adult animals.