Nuclear calcium-activated gene expression: possible roles in neuronal plasticity and epileptogenesis

Nuclear calcium signals associated with electrical activation of neurons are critical regulators of gene expression and may cause changes in neuronal structure and function. Recent studies have identified a key component of the transcriptional machinery, the coactivator CREB binding protein (CBP), as a target for a nuclear calcium signalling pathway. Because the regulation of many genes involves transcription factors that function through their interaction with CBP, this mechanism, termed 'the coactivator control model', may modulate the expression of a large number of genes. During normal working of the brain, nuclear calcium increases may be transient and initiate transcriptional responses that are important for learning and memory. However, more intense or sustained stimulations of neurons (for example those used in the kindling model) may overactivate nuclear calcium-regulated processes. This may initiate inappropriate gene expression responses and could lead to the formation of epileptic neuronal circuits and disorders of neuronal excitability.