Abstract

Activity-dependent plastic changes in the strength of synaptic connections are considered to underlie learning and memory. Activation of neurons by a variety of stimuli influences the level of expression of the immediate-early gene c-fos, and the heterodimer of the gene product, Fos, regulates transcription of other genes. Therefore, Fos is regarded as a mediator by which brief stimuli trigger long-term changes in the synaptic connections. Here we show that Fos expression in the CA3 region of the hippocampus may be obligatory for spatial memory formation in a radial arm maze test. Fos-positive cells increased in the cerebral cortices and the CA3 region of the dorsal hippocampus during the course of radial arm maze training in rats. Inhibition of Fos expression in this region of the hippocampus, but not the cingulate and motor cortex, by means of antisense oligonucleotide treatment resulted in an impairment of spatial memory formation. Our results support the hypothesis that the inducible transcription factor c-fos is essential for encoding spatial memory.

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