To understand the cellular processes involved in learning and memory, the cellular responses of neurons to calcium (Ca2+) signals, which can be evoked via synaptic activity, should be examined. A series of investigations in primary cultures of neurons revealed that the regulation of brain-derived neurotrophic factor (BDNF) mRNA expression is mediated by almost the same Ca2+ signaling pathways as that of c-fos mRNA expression. Such early co-activation of both genes in response to Ca2+ signals further suggests that sets of calcium-responsive genes (CaRGs) are concurrently activated by Ca2+ signals. The products encoded by CaRGs should then evoke a variety of physiological responses in neurons with the expression of another set of genes, the products of which are directly involved in the outcomes of neuronal functions. Thus, a cascade of gene expression can be induced by Ca2+ signals evoked via synaptic activity. It is of particular interest to identify the CaRGs and investigate the regulational mechanisms of their expression. A cellular approach using primary cultures of neurons would therefore lead to a better understanding of the intracellular processes involved in learning and memory.