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 language | English (US) |
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Pages (from-to) | 6304-6314 |
Number of pages | 11 |
Journal | Journal of Neuroscience |
Volume | 23 |
Issue number | 15 |
DOIs | |
State | Published - Jul 16 2003 |
Externally published | Yes |
Keywords
- CREB
- Conditioned taste aversion
- Fear conditioning
- Hippocampus
- LTD
- LTP
- Learning
- Memory
- Synaptic plasticity
- Water maze
ASJC Scopus subject areas
- General Neuroscience