Schematic of processes regulating cytoskeletal dynamics during LTP stabilization. The proposed model shows signaling cascades that regulate distinct stages of dendritic spine actin reorganization. Activity-driven RhoA to cofilin signaling, leading to F-actin assembly, is rapid (∼2 min) and A1R sensitive. Evidence from other systems suggests that A1R inhibits RhoA through a GTPase-activating protein (GAP). Parallel activation of PAK via Rac is adenosine insensitive and influences later (>10 min) LTP consolidation events. The dashed PAK to LIM kinase (LIMK) arrow denotes signaling, shown in neurons and other cell systems, that does not appear to be involved in synaptic potentiation or its concomitant actin polymerization. Rather, results in this study suggest that LTP-related PAK signaling regulates proteins involved in higher order organization of the spine cytoskeleton. The independence of the described signaling pathways and their functional roles in LTP suggest that activity-induced cytoskeletal reorganization has distinct and sequential stages involving RhoA and then Rac signaling. NMDAR, NMDA receptor.