This study identified nuclear calcium as one of the most potent regulators of neuronal gene expression and uncovered a large pool of 185 nuclear calcium-regulated genes. Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. Calcium signaling in synapse-to-nucleus communication. The versatility and universality of calcium signalling. The modulation of nuclear calcium signalling may be a novel therapeutic strategy for the treatment of neurological disorders.īerridge, M. The effects of nuclear calcium on gene regulation and neuroprotection are antagonized by the stimulation of extrasynaptic NMDA receptors that trigger transcriptional shut-off and cell death pathways.ĭysfunctioning of nuclear calcium signalling, referred to as 'nuclear calciopathy', may be a common factor in the aetiology of neurodegenerative and neuropsychiatric conditions. The neuroprotective activity of nuclear calcium signalling appears to be mediated by a set of genes that render mitochondria more resistant to harmful conditions. The target gene pool of nuclear calcium signalling comprises nearly 200 genes that function, for example, in the regulation of dendrite architecture and spine density and shape. It controls the activity or nuclear localization of several transcriptional regulators (which include CREB (cyclic AMP-responsive element-binding protein), CBP (CREB-binding protein), class IIa HDACs (histone deactylases) and MECP2 (metyhyl-CpG-binding protein 2)) that either generate or interpret chromatin modifications. Nuclear calcium is one of the most potent regulators of gene expression. Nuclear calcium transients may also be initiated or enhanced by calcium release from intracellular calcium stores mediated by inositol triphosphate or ryanodine receptors. The mechanism through which synaptic activity leads to increases in the intranuclear calcium concentration involves stimulation of synaptic NMDA receptors, generation of backpropagating action potentials and the opening of voltage-gated calcium channels.

The requirement of nuclear calcium signals for long-term memory formation is evolutionarily conserved from flies to mammals. It serves as a signalling end point in synapse-to-nucleus communication and activates gene programmes needed for the long-term implementation of many neuroadaptations, including memory consolidation, acquired neuroprotection and the development of chronic pain. Nuclear calcium is an important mediator of activity-dependent gene expression in the nervous system.

Calcium entry in neurons dendrite