Fragmentation of the Golgi is observed in several neurodegenerative diseases. The Golgi plays key functions in trafficking and posttranslational processing of proteins destined for the cell surface or secretion, including those proteins localized to synapses. Thayer et al. used immunofluorescence tracking of Golgi markers in cultured hippocampal neurons and observed that conditions that caused hyperexcitability (depolarization with increased potassium ions in the medium) or hyperactivity (inhibition of GABA signaling with bicuculline or withdrawal of the glutamate receptor antagonist APV) triggered Golgi fragmentation that was reversible after the neurons were returned to normal medium. Experiments with tetrodotoxin to block action potentials showed that synaptic activity was required for the Golgi fragmentation. Inhibition of calcium-calmodulin kinase with KN-93 prevented bicuculline-induced Golgi fragmentation, whereas inhibition of protein phosphatases PP2A and PP1 with okadaic acid triggered Golgi fragmentation in the absence of neuronal hyperactivity. The functional or pathological consequences of such Golgi fragmentation remain to be established, but these results indicate that neuronal activity serves as a signal to the Golgi.