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Learn Mem. 2016 Nov 15;23(12):714-722. doi: 10.1101/lm.042044.116. Print 2016 Dec.

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

Author information

1
Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA.
2
Center for Neural Science, New York University, New York, New York 10003, USA.
3
Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA John.H.Byrne@uth.tmc.edu.

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.

PMID:
27918277
PMCID:
PMC5110990
DOI:
10.1101/lm.042044.116
[Indexed for MEDLINE]
Free PMC Article

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