Does cAMP Response Element-Binding Protein Have a Pivotal Role in Hippocampal Synaptic Plasticity and Hippocampus-Dependent Memory?

• Published in: The Journal of neuroscience 2003-07, Vol.23 (15), p.6304-6314
• Main Authors: Balschun, Detlef, Wolfer, David P, Gass, Peter, Mantamadiotis, Theo, Welzl, Hans, Schutz, Gunther, Frey, Julietta U, Lipp, Hans-Peter
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - physiology; Behavioral/Systems/Cognitive; Conditioning (Psychology); Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Electric Stimulation; Fear - physiology; Gene Dosage; Gene Targeting - methods; Hippocampus - metabolism; Hippocampus - physiology; In Vitro Techniques; Long-Term Potentiation - genetics; Long-Term Potentiation - physiology; Long-Term Synaptic Depression - genetics; Long-Term Synaptic Depression - physiology; Maze Learning - physiology; Memory - physiology; Mice; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Protein Isoforms - deficiency; Protein Isoforms - genetics; Protein Isoforms - metabolism; Taste - genetics; Taste - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.23-15-06304.2003

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.