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There is controversial evidence that neocortical projections to the neostriatum may regulate the neostriatal expression of the proenkephalin ( PEnk ) gene. Therefore, we have studied  PEnk  gene expression in organotypic neocortico-neostriatal co-cultures as well as cultures of isolated neostriata.  PEnk  mRNA was determined with  in situ  hybridization. Removal of the neocortex caused a time-dependent reduction in the number of neostriatal cells which showed expression of the  PEnk  gene. A maximal decrease was seen after 3 days. Within 2 days after blockade of glutamate receptors of the NMDA type significantly fewer neostriatal cells expressed the PEnk gene, indicating that NMDA receptors mediated the expression of the gene. In isolated neostriatal slices in which the expression of the  PEnk  gene had been down-regulated, NMDA increased the number of cells which expressed the gene in a time-dependent manner. Maximal expression was observed after 3 days. This induction was reduced by nimodipine, which blocks L-type Ca 2+ -channels. The slow increase in  PEnk  gene expression caused by NMDA resembled a recruiting process. It seems to be specific for the neostriatum and may be due to the latter's neuronal organization.

Neocortical Projections Regulate the Neostriatal Proenkephalin Gene Expression