Activity-dependent changes in the mammalian brain are important for memory consolidation, but the intracellular processes undergoing such changes remain poorly understood. We report here that learning causes biphasic changes in microtubule stability in the dentate gyrus of hippocampus. Pharmacological manipulations of microtubule stability and instability altered fear memory, suggesting an important role of microtubule stability in memory. We identify stathmin as a regulator of learning-induced changes in microtubule stability, which in turn mediate dendritic transport of the GluA2 subunit of AMPA receptors. Stathmin mutations disrupted learning-induced changes in dentate gyrus microtubule stability, dendritic transport of the GluA2, long-term potentiation and long-term memory. Blocking GluA2 endocytosis rescued memory deficits in stathmin mutant mice. We also found that memory loss in aged mice is associated with deficit in GluA2 dendritic transport by changing stathmin-mediated control of microtubule stability. Thus, stathmin-microtubule-dependent GluA2 dendritic transport represents a novel signaling pathway critical for memory formation.