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    Keywords: brain ; Germany ; LONG-TERM ; GENE ; PROTEIN ; transcription ; TRANSCRIPTION FACTOR ; REDUCTION ; WATER ; MEMORY ; FORM ; CAMP ; CELL-SURVIVAL ; conditioned taste aversion ; CONDITIONED TASTE-AVERSION ; CREB ; DEFICITS ; DELETION ; ELEMENT ; ELEMENT-BINDING PROTEIN ; ELEMENT-BINDING-PROTEIN ; fear conditioning ; hippocampus ; ISOFORM ; ISOFORMS ; knockout ; LATE-PHASE ; learning ; LONG-TERM POTENTIATION ; LTD ; LTP ; MAP KINASE ; MOUSE ; MOUSE-BRAIN ; MUTANT ; NERVOUS-SYSTEM ; NO ; PERFORMANCE ; PROBE ; RESPONSE ELEMENT ; score ; STAGE ; synaptic plasticity ; TARGETED MUTATION ; TRANSCRIPTION FACTORS ; TRANSGENIC MICE ; TRIAL ; TRIALS ; WATER MAZE
    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
    Type of Publication: Journal article published
    PubMed ID: 12867515
    Signatur Availability
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