CaMKII requirement for the persistence of in vivo hippocampal mossy fiber synaptic plasticity and structural reorganization

- CaMKII is necessary for the maintenance of in vivo LTP at adult MF-CA3 pathway.
- CaMKII is required for activity-dependent morphological reorganization at MF.
- CaMKII is a key molecule for the maintenance of synaptic plasticity underlying memory persistence.

CaMKII has been proposed as a molecular substrate for long-term memory storage due to its capacity to maintain an active autophosporylated state even after the decay of the external stimuli. The hippocampal mossy fiber-CA3 pathway (MF-CA3) is considered as a relevant area for acquisition and storage of different learning tasks. MF-CA3 pathway exhibits a form of LTP characterized by a slow initial increase in the EPSP slope that is independent of NMDA receptors activation. Our previous studies show that application of high frequency stimulation sufficient to elicit MF-CA3 LTP produces structural reorganization, in a manner independent of LTP induction, at the stratum oriens of hippocampal CA3 area 7 days after stimulation. However, the molecular mechanisms that underlie the maintenance of MF-CA3 LTP as well as the concomitant structural reorganization in this area remain to be elucidated. Here we show that acute microinfusion of myr-CaMKIINtide, a noncompetitive inhibitor of CaMKII, in the hippocampal CA3 area of adult rats during the late-phase of in vivo MF-CA3 LTP blocked its maintenance and prevented the accompanying morphological reorganization in CA3 area. These findings support the idea that CaMKII is a key molecular substrate for the long-term hippocampal synaptic plasticity maintenance.