Mice with a fra−1 knock−in into the c−fos locus show impaired spatial but regular contextual learning and normal LTP

Abstract 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.