High-frequency discharge of dentate granule cells, but not long-term potentiation, induces c-fos protein.

Competence genes, such as c-fos, may play key roles in information storage in the nervous system by linking relatively brief extracellular signals to long-term changes in the neuron. In support of this idea we, and others, have shown that the c-fos protein occurs in adult mammalian neurons and that higher levels of the protein are induced in certain brain regions after kindled or metrazol-induced seizures in mice and rats, sensory stimulation and mechanical damage in spinal cord neurons, and after depolarization in PC12 cells. Here we report that a massive induction of c-fos protein is observed in dentate granule cells in four conditions that result in repetitive firing: localized seizure discharges; high frequency antidromic activation; orthodromic activation in the presence of iontophoresed bicuculline; and frequency potentiation. However, stimulation of the perforant path with high frequency trains that produced long-term potentiation at the perforant path-granule cell synapse did not reliably induce c-fos in the dentate gyrus. These findings suggest that c-fos induction can follow repetitive neuronal discharge but is not involved in long-term potentiation.