title: Computational model of a positive BDNF feedback loop in hippocampal neurons following inhibitory avoidance training.
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.
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA.
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, USA John.H.Byrne@uth.tmc.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D003198:Computer Simulation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D022782:CCAAT-Enhancer-Binding Protein-beta; C545014:Cebpb protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger