Transient Photoactivation of Rac1 Induces Persistent Structural LTP Independent of CaMKII in Hippocampal Dendritic...

Structural changes in dendritic spines underlie long-term potentiation (LTP). While CaMKII has been considered as the primary driver of these changes, we show that transient, localized activation of Rac1 alone is sufficient to induce structural LTP in hippocampal slices prepared from rat pups of either sex. Using photoactivatable Rac1 (PA-Rac1), we demonstrated that Rac1 activation triggers spine enlargement and actin polymerization. This PA-Rac1-induced plasticity was blocked by Rac1 and Pak1 inhibitors but not by a CaMKII inhibitor. Our results identify Rac1 as an upstream of persistent signaling that stabilizes actin-based spine structural changes critical for synaptic memory encoding.