Previous work from our laboratory demonstrated that the RNA-binding protein HuD binds to and stabilizes the GAP-43 mRNA. In this study, we characterized the expression of HuD and GAP-43 mRNA in the hippocampus during two forms of neuronal plasticity. During post-natal development, maximal expression of both molecules was found at P5 and their levels steadily decreased thereafter. At P5, HuD was also present in the subventricular zone, where it co-localized with doublecortin. In the adult hippocampus, the basal levels of HuD and GAP-43 were lower than during development but were significantly increased in the dentate gyrus after seizures. The function of HuD in GAP-43 gene expression was confirmed using HuD-KO mice, in which the GAP-43 mRNA was significantly less stable than in wild type mice. Altogether, these results demonstrate that HuD plays a role in the post-transcriptional control of GAP-43 mRNA in dentate granule cells during developmental and adult plasticity.