A stimulation inducing long-term potentiation (LTP) of synaptic transmission induces a persistent expansion of dendritic spines, phenomena recognized as structural LTP (sLTP). Actin cytoskeleton plays an essential role in this process. We previously proposed the persistent interaction between CaMKII and Tiam1, an activator of Rac is a critical mediator of actin regulation. Interestingly, the formation of the complex locks CaMKII into an active conformation, which in turn maintains the activity of Tiam1 though phosphorylation. This makes Rac1 activity persist in a stimulated spine. Therefore, the CaMKII-Tiam1 complex plays a pivotal role in sLTP.

To understand the significance of the CaMKII-Tiam1 complex in vivo, we generated Tiam1 knocked-in mice where critical residues for CaMKII binding were mutated into alanines. In the KI brain, Rac1 activity was specifically reduced compared with WT littermate. Also sLTP was abolished in hippocampal neurons from KI. Gross appearance of brain structure and spine density was normal in KI mice. The KI mice showed decreased object recognition memory 7 days after training while the other behavioral tests were normal. Thus, the CaMKII-Tiam1 interaction is not only crucial for sLTP but also requires for memory storage.