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Activity‐dependent changes in synapses rely on functional changes in resident proteins and on gene expression. We addressed the relationship between synapse activity and the expression of synaptic genes by comparing RNA levels in the neocortex of normal mice versus secretion‐deficient and therefore synaptically silent munc18‐1 (mammalian homologue of Caenorhabditis elegans uncoordinated locomotion‐18) null mutants, using microarray expression analysis, real‐time quantitative PCR and northern blotting. We hypothesized that genes under the control of synaptic activity would be differentially expressed between mutants and controls. We found that few synaptic genes were differentially expressed. However, most neuropeptide genes with detectable expression on the microarray were differentially expressed, being expressed 3–20‐fold higher in control cortex. Several other secreted proteins were …