Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) N.Y.), 2016-12, Vol.23 (12), p.714-722
• Main Authors: Zhang, Yili, Smolen, Paul, Alberini, Cristina M, Baxter, Douglas A, Byrne, John H
• Format: Article
• Language: English
• Subjects: Animal Behavior; Animals; Brain Hemisphere Functions; Brief Communication; Equations (Mathematics); Feedback (Response); Inhibition; Memory; Molecular Structure; Simulation; Training
• ISSN: 1072-0502; 1549-5485; 1549-5485
• DOI: 10.1101/lm.042044.116

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 ß isoform of the CCAAT/enhancer binding protein (C/EBPß). Increased levels of C/EBPß lead to increased "bdnf" expression. Simulations predicted that an empirically observed delay in the BDNF-pCREB-C/EBPß 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/EBPß feedback loop contribute to consolidation. Currently, the nature of these downstream pathways is unknown.