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J Neurosci. 2014 Sep 10;34(37):12547-59. doi: 10.1523/JNEUROSCI.0324-14.2014.

A positive autoregulatory BDNF feedback loop via C/EBPβ mediates hippocampal memory consolidation.

Author information

1
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.
2
Center for Neural Science, New York University, New York, New York 10003 and.
3
Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
4
Center for Neural Science, New York University, New York, New York 10003 and ca60@nyu.edu.

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.

KEYWORDS:

BDNF; C/EBP; consolidation; hippocampus; memory; memory persistence

PMID:
25209292
PMCID:
PMC4160783
DOI:
10.1523/JNEUROSCI.0324-14.2014
[Indexed for MEDLINE]
Free PMC Article

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