Computational model of a positive BDNF feedback loop in hippocampal neurons following inhibitory avoidance training. uri icon

abstract

  • Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins with an IA-induced release of brain-derived neurotrophic factor (BDNF), which in turn leads to rapid phosphorylation of the cAMP response element-binding protein (pCREB), and a subsequent increase in the level of the isoform of the CCAAT/enhancer binding protein (C/EBP). Increased levels of C/EBP lead to increased bdnf expression. Simulations predicted that an empirically observed delay in the BDNF-pCREB-C/EBP feedback loop has a profound effect on the dynamics of consolidation. The model also predicted that at least two independent self-sustaining signaling pathways downstream from the BDNF-pCREB-C/EBP feedback loop contribute to consolidation. Currently, the nature of these downstream pathways is unknown.

published proceedings

  • Learn Mem

altmetric score

  • 7

author list (cited authors)

  • Zhang, Y., Smolen, P., Alberini, C. M., Baxter, D. A., & Byrne, J. H.

citation count

  • 18

complete list of authors

  • Zhang, Yili||Smolen, Paul||Alberini, Cristina M||Baxter, Douglas A||Byrne, John H

publication date

  • December 2016