Rac1 Constrains Memory Consolidation.

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase that regulates actin cytoskeleton dynamics and synaptic plasticity. Rac1 has been implicated in active forgetting, but whether it also constrains the consolidation of new memories remains unclear. Here we show that systemic administration of the Rac1 inhibitor 1A-116 after training in the novel object recognition task markedly extends memory persistence in rats. A single post-training injection of 1A-116 enhanced recognition memory for at least 28 d without altering locomotor- or anxiety-related behaviors. When given after a brief, subthreshold training session that normally supports only short-term memory, 1A-116 enabled long-term retention that required hippocampal protein synthesis. This promnesic effect was time-dependent, independent of sex, and consistent with Rac1 acting as a negative regulator of memory consolidation rather than merely promoting forgetting. These findings indicate that Rac1 activity after learning limits the consolidation process itself, functioning as a molecular brake on recognition memory stabilization, and suggest that its inhibition may represent a therapeutic avenue to enhance cognitive durability in both healthy and pathological conditions.