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

Dhananjay Bambah-Mukku, Alessio Travaglia, Gabriella Pollonini, Cristina M. Alberini, Dhananjay Bambah-Mukku, Dillon Y. Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)12547-12559
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number37
DOIs
StatePublished - Sep 10 2014

Keywords

  • BDNF
  • C/EBP
  • Consolidation
  • Hippocampus
  • Memory
  • Memory persistence

ASJC Scopus subject areas

  • Neuroscience(all)

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