Immunohistochemistry of c-fos in Mouse Brain During Postnatal Development: Basal Levels and Changing Response to Metrazol and Kainate Injection.

Levels and cellular distribution of FOS, the product of c-fos (onco)gene, were studied by immunohistochemistry during the development of mouse brain at rest and after the administration of convulsants. Basal FOS immunoreactivity became detectable only after postnatal day 20 (P20). Metrazol and kainate at the appropriate doses induced convulsions at all ages but, in both cases, FOS accumulated in limbic areas (particularly in the dentate gyrus) only after a certain age: P20 for kainate and P30 for Metrazol. Surprisingly, considering the different molecular targets of Metrazol and kainate, respectively, and the different type of convulsions elicited, the cell groups in the limbic areas in which FOS increased were the same in the two cases. These results suggest that both drugs produced FOS increase by finally activating the same circuit. During ontogeny, the ability to accumulate FOS, which appears after P20, could be the sign of the attained maturity of signal transduction mechanisms in the cells of the hippocampal formation; endogenous signals originating from the activity of the nervous system increase the basal FOS levels and exogenous signals (i.e. like those given, probably locally, by kainate) further increase these levels. Metrazol manifests its capability to induce FOS accumulation only at later ages. We suggest that this occurs because the Metrazol target is probably distant from the hippocampal region and thus the maturity of a nerve pathway(s) is also required for c-fos induction.