Memory storage in mammalian neurons probably depends on both biochemical ev
ents and morphological alterations in dendrites. Here we report an activity
-dependent stabilization of the MAP kinase (MAPK) pathway, prominent in hip
pocampal dendrites. The longevity of the signal in these dendrites was incr
eased to hours when multiple spaced stimuli were used. Likewise, spaced sti
muli and MAPK activation were critical for protrusion of new dendritic filo
podia that also remained stable for hours. Our experiments define a new rol
e for stimulus-specific responses of MAPK signaling in activity-dependent n
euronal plasticity. The local biochemical signaling in dendrites complement
s MAPK signaling in gene expression. Together, these processes may support
long-lasting behavioral changes.