title: A positive autoregulatory BDNF feedback loop via C/EBPβ mediates hippocampal memory consolidation.
abstract: Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003 and Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Dhananjay
authors.identifier: http://orcid.org/0000-0001-5822-6326
authors.initials: D
authors.lastname: Bambah-Mukku
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003 and.
authors.forename: Alessio
authors.initials: A
authors.lastname: Travaglia
authors.affiliation: Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Dillon Y
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003 and.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pollonini
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003 and ca60@nyu.edu.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007266:Inhibition, Psychological; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D022782:CCAAT-Enhancer-Binding Protein-beta; C545014:Cebpb protein, rat
keywords: BDNF; C/EBP; consolidation; hippocampus; memory; memory persistence