Abstract: Neurons undergo activity-dependent changes in their molecular composition and structure in order to regulate cellular processes such as dendritic growth, synapse elimination, spine maturation and synaptic strength. Such synaptic plasticity plays an important role during a critical period in brain development and contributes to sensory adaptation and to learning and memory in the mature nervous system. Its dysregulation underlies a number of pathological processes in psychiatric and neurodegenerative disorders, such as addiction, depression, anxiety, schizophrenia, epilepsy and traumatic brain injury. Short-term activity-dependent synaptic changes rely mostly on post-translational modifications of pre-existing proteins, whereas the long-term maintenance of synaptic adaptations depends on gene induction. Signals from the synapse to the nucleus activate gene expression. Such signals are thought to be encoded in calcium waves or conveyed by macromolecular signaling complexes translocated retrogradely by motor proteins. The induced gene transcription and protein synthesis alters the composition of synaptic protein networks and provides a mechanism for translating synaptic activity into persistent synaptic changes. In accordance, large sets of genes whose expression levels are regulated by synaptic activity have been described in the past decades. As expected, several of these genes encode proteins that modulate synaptic function and play a role in neuronal plasticity-related processes. However, it has to be considered that altered gene expression levels are only part of the complex activity-regulated transcriptional signature. Alternative splicing, the differential inclusion and exclusion of exonic sequence, in combination with other related processes such as the use of alternative transcriptional initiation sites and alternative polyadenylation sites as well as mRNA editing ensure the transcriptomic and proteomic diversity required for the regulation and diversification of synaptic functions.