The present address of Anna Pokorska is Biofocus Science Park, Milton Road, Cambridge, CB4 0FG, England.
Synaptic activity induces signalling to CREB without increasing global levels of cAMP in hippocampal neurons
Article first published online: 13 JAN 2003
Journal of Neurochemistry
Volume 84, Issue 3, pages 447–452, February 2003
How to Cite
Pokorska, A., Vanhoutte, P., Arnold, F. J. L., Silvagno, F., Hardingham, G. E. and Bading, H. (2003), Synaptic activity induces signalling to CREB without increasing global levels of cAMP in hippocampal neurons. Journal of Neurochemistry, 84: 447–452. doi: 10.1046/j.1471-4159.2003.01504.x
- Issue published online: 13 JAN 2003
- Article first published online: 13 JAN 2003
- Received February 18, 2002; revised manuscript received June 28, 2002; accepted September 18, 2002.
- nuclear calcium;
- signal transduction;
- synaptic activity;
Nuclear calcium signals associated with electrical activation of neurons can control the activity of the transcription factor cAMP-response element binding protein (CREB). Yet, cAMP is thought to be the key messenger that links synaptic activity to the regulation of CREB-mediated transcription. It is generally assumed that synaptic activity increases the intracellular levels of cAMP; this causes activation of the cAMP-dependent protein kinase (PKA) that regulates CREB-mediated transcription either directly or through controlling nuclear signalling of the MAP kinases/extracellular signal-regulated kinases (ERK1/2) pathway. Here we show that, in hippocampal neurons, synaptic activity failed to increase global levels of cAMP that would be required for the cAMP-PKA system to induce nuclear events. Even near-continuous bursting of action potentials, giving rise to large nuclear calcium signals and robust CREB-dependent transcription, left global intracellular levels of cAMP unchanged. These results suggest that the cAMP-PKA system does not function as the transducer of synaptic signals to the nucleus. They indicate that the known inhibitory effects of blockers of PKA on gene expression and long-lasting plasticity triggered by calcium entry reflect a gating function of basal activity of PKA that renders neurons permissive for nuclear calcium-regulated, CREB/CBP-dependent gene expression.