title: Transcription-dependent neuronal plasticity: The nuclear calcium hypothesis.
abstract: In neurons, calcium ions control gene transcription induced by synaptic activity. The states and histories of neuronal activity are represented by a calcium code that comprises the site of calcium entry, and the amplitude, duration and spatial properties of signal-evoked calcium transients. The calcium code is used to transform specific firing patterns into qualitatively and quantitatively distinct transcriptional responses. The following hypothesis is proposed: electrical activity causes long-lasting, transcription-dependent changes in neuronal functions when synaptically evoked calcium transients associated with the stimulation propagate to the nucleus; gene transcription activated by dendritic calcium signals only is insufficient to consolidate functional alterations long-term. Similar to enduring increases in synaptic efficacy, nuclear calcium transients are induced by high-frequency firing patterns or by weak synaptic inputs coinciding with backpropagating dendritic action potentials. Nuclear calcium stimulates CREB-mediated transcription and, through inducing the activity of the transcriptional coactivator CREB-binding protein (CBP), may modulate the expression of numerous genes including neurotransmitter receptors and scaffolding proteins. Increases in the transcription rate of target genes are predicted to be transient and in many cases small, however, they collectively contribute to the maintenance of changes in synaptic efficacy. Nuclear calcium may be the common regulator of diverse transcription-dependent forms of neuronal plasticity.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, England. hb1@mrc-lmb.cam.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Bading
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D009473:Neuronal Plasticity; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D002118:Calcium