Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.
The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.
Gass
Peter
P
Central Institute of Mental Health Mannheim, University of Heidelberg, J 5 D-68159 Mannheim, Germany. gass@as200.zi-mannheim.de
Fleischmann
Alexander
A
Hvalby
Oivind
O
Jensen
Vidar
V
Zacher
Christiane
C
Strekalova
Tatyana
T
Kvello
Ane
A
Wagner
Erwin F
EF
Sprengel
Rolf
R
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency* / Q000235:genetics*; D011930:Reaction Time / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D013037:Spatial Behavior / Q000502:physiology*; D013997:Time Factors; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1