Activity-dependent synaptic modification must occur specifically to preserve the large information storage capacity of neurons. Since long-term changes in synaptic strength require gene expression and new protein synthesis we consider the role that gene expression plays in the specificity of synaptic modification. Ca2+ influx is essential for transducing synaptic activity into gene expression. Different temporal profiles of increased global Ca2+ and different types of Ca2+ channel have been demonstrated to produce different effects in the nucleus. It is possible therefore that synaptic activity may produce different programs of gene expression which may in turn control specific long-term changes in synaptic strength. We review recent data which suggest that the spatial properties of Ca2+ influx may provide a mechanism for the selective activation of molecules which signal to the nucleus. In particular, we describe data which suggests that Ca2+ channels may function in signal complexes at the synapse to propagate signals that contribute to distinct nuclear responses.