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

• Author / Creator

  Maity, Sabyasachi

• 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.

• Subjects / Keywords

  • Long-term potentiation
  • Epigenetic modifications
  • Hippocampus
  • Norepinephrine

• Graduation date

  Spring 2014

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3FF3M760

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.