Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory?

Detlef Balschun, David P. Wolfer, Peter Gass, Theo Mantamadiotis, Hans Welzl, Günther Schütz, Julietta U. Frey, Hans Peter Lipp

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

Previous studies addressing the role of the transcription factor cAMP response element-binding protein (CREB) in mammalian long-term synaptic plasticity and memory by gene targeting were compromised by incomplete deletion of the CREB isoforms. Therefore, we generated conditional knock-out strains with a marked reduction or complete deletion of all CREB isoforms in the hippocampus. In these strains, no deficits could be detected in lasting forms of hippocampal long-term potentiation (LTP) and long-term depression (LTD). When tested for hippocampus-dependent learning, mutants showed normal context-dependent fear conditioning. Water maze learning was impaired during the early stages, but many mutants showed satisfactory scores in probe trials thought to measure hippocampus-dependent spatial memory. However, conditioned taste aversion learning, a putatively hippocampus-independent memory test, was markedly impaired. Our data indicate that in the adult mouse brain, loss of CREB neither prevents learning nor substantially affects performance in some hippocampus-dependent tasks. Furthermore, it spares LTP and LTD in paradigms that are sensitive enough to detect deficits in other mutants. This implies either a species-specific or regionally restricted role of CREB in the brain and/or a compensatory upregulation of the cAMP response element modulator (CREM) and other as yet unidentified transcription factors.

Original languageEnglish (US)
Pages (from-to)6304-6314
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number15
DOIs
StatePublished - Jul 16 2003

Keywords

  • CREB
  • Conditioned taste aversion
  • Fear conditioning
  • Hippocampus
  • LTD
  • LTP
  • Learning
  • Memory
  • Synaptic plasticity
  • Water maze

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Balschun, D., Wolfer, D. P., Gass, P., Mantamadiotis, T., Welzl, H., Schütz, G., Frey, J. U., & Lipp, H. P. (2003). Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory? Journal of Neuroscience, 23(15), 6304-6314. https://doi.org/10.1523/jneurosci.23-15-06304.2003