The clathrin-assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin-assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity. Published by Elsevier Inc.