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

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

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)714-722
Number of pages9
JournalLearning and Memory
Volume23
Issue number12
DOIs
StatePublished - Dec 2016

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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