NOREPINEPHRINE-MEDIATED SYNAPTIC PLASTICITY: A NOVEL SIGNALING DIALOGUE BETWEEN RECEPTORS AND NUCLEUS Open Access

[摘要] Norepinephrine (NE) helps in the consolidation and retention of memories of emotionally charged events. However, the pathway from membrane receptors to nucleus in noradrenergic signaling in the brain is not completely understood. The cyclic AMP-PKA pathway is one of the most studied signaling pathways recruited by norepinephrine to induce and maintain LTP, a cellular correlate of long term memory. In the present study, I describe a novel signaling mechanism of NE-mediated induction and expression of LTP when paired with a specific stimulus protocol, through cAMP receptors (Epac) instead of PKA. I demonstrate that this pathway involves transcriptional and epigenetic mechanisms other than local protein synthesis. Hence, this unique pathway may be recruited upon novel experience to form a stable memory. Considering that many memory-related cognitive impairments are due to altered pathophysiology of the noradrenergic system, these results both increase our understanding and move us closer to a possible solution for neurological diseases involving neuromodulators like NE.

[发布机构] University of Alberta

[效力级别] Epigenetic modifications