Nuclear Ca2+ and the cAMP response element-binding protein family mediate a late phase of activity-dependent
Sofia Papadia1, Patrick Stevenson, Neil R Hardingham
1Centre for Neuroscience Research, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom.
Abstract:
The mechanism by which physiological synaptic NMDA receptor activity promotes neuronal survival is not well understood. Here, we show that that an episode of synaptic activity can promote neuroprotection for a long time after that activity has ceased. This long-lasting or "late phase" of neuroprotection is dependent on nuclear calcium signaling and cAMP response element (CRE)-mediated gene expression. In contrast, neuroprotection evoked acutely by ongoing synaptic activity relies solely on the activation of the phosphatidylinositol 3-kinase/Akt pathway. This "acute phase" does not require nuclear calcium signaling and is independent of activation of the CRE-binding protein (CREB) family of transcription factors. Thus, activity-dependent neuroprotection comprises two mechanistically distinct phases that differ in their spatial requirements for calcium and in their reliance on the CREB family.
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