Strong inputs to neurons trigger complex biochemical events leading to synaptic plasticity. These biochemical events occur at many spatial scales, ranging from submicron dendritic spines to signals that propagate hundreds of microns from dendrites to the nucleus. ERKII is an important signaling molecule that is involved in many aspects of plasticity, including local excitability, communication with the nucleus, and control of local protein synthesis. We observed that ERKII activation spreads long distances in apical dendrites of stimulated hippocampal CA1 pyramidal neurons. We combined experiments and models to show that this >100 mum spread was too large to be explained by biochemical reaction-diffusion effects. We show that two modes of calcium entry along the dendrite contribute to the extensive activation of ERKII. We predict the occurrence of feedback between biophysical events resulting in calcium entry, and biochemical events resulting in ERKII activation. This feedback causes a switch-like propagation of ERKII activation, coupled with enhanced electrical excitability, along the apical dendrite. We propose that this propagating switch forms zones on dendrites in which plasticity is facilitated.