Calcium entry into neuronal cells through N-methyl-D-aspartate (NMDA)-type glutamate receptors or L-type voltage-gated calcium channels is a key event in the control of gene expression following electrical activation. Calcium acts both in the cytoplasm and the nucleus to activate signalling pathways that stimulate gene expression through different DNA regulatory elements. Differential control of transcription by spatially distinct calcium signals provides a mechanism by which a single second messenger can generate diverse transcriptional responses. This may allow for stimulation-specific modulation of gene expression critical for adaptive changes in the nervous system.