Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory?
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.
Balschun
Detlef
D
Department of Neurophysiology, Leibniz Institute for Neurobiology, 39108 Magdeburg, Germany. balschun@ifn-magdeburg.de
Wolfer
David P
DP
Gass
Peter
P
Mantamadiotis
Theo
T
Welzl
Hans
H
Schütz
Günther
G
Frey
Julietta U
JU
Lipp
Hans-Peter
HP
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003213:Conditioning, Psychological; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism*; D004558:Electric Stimulation; D005239:Fear / Q000502:physiology; D018628:Gene Dosage; D018390:Gene Targeting / Q000379:methods; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000235:genetics / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D020033:Protein Isoforms