Plasticity at excitatory hippocampal synapses and CaMKII as a molecular memory molecule

The hippocampus has been the preferred site for studying synaptic plasticity because of the enormous importance this region has in the formation and retention of episodic memory. Over three decades of work have gone into understanding the mechanisms behind changes in synaptic strength that underlie our ability to learn new experiences. The very circuitry of the hippocampus is set up to greatly enhance the ability to learn, as evidenced by monoaminergic modulation that can regulate the flow of relevant information through this region. It is then up to the appropriate synapses to appropriately maintain the saliency of experience, such that it is reflected in the strength of the connections between neurons.; The induction of LTP causes numerous biochemical cascades to become activated in post-synaptic cells. We report that application of an adenylyl cyclase activator, a phosphodiesterase inhibitor, and activation of the NMDA type receptor is sufficient to produce a form of chemical LTP. Furthermore, this cLTP induces persistent translocation of CaMKII to spines located on the dendrites of postsynaptic cells. We have developed a new method for quantifying the amount of bound protein at individual synaptic spines. We report that even under basal conditions, spines tend to accumulate CaMKII, and the amount of accumulation correlates with both the volume and strength of that particular spine. Further results show a moderate decrease in bound CaMKII at spines when we interfere with binding to the NMDA receptor, and a larger decrease when F-actin is depolymerized. Although CaMKII is well known for its role in the induction of LTP, it now appears CaMKII may have a long-term role in maintaining synaptic strength and synaptic size due to its structural interactions. Here, we have addressed how one protein, CaMKII, is related to the size and strength of spines, such that it may indeed act as a synaptic memory molecule.