Dopaminergic regulation of transcription factor expression in organotypic cultures of developing striatum

Abstract

Dopamine is a major neurotransmitter in neural systems innervating the striatum, and dopamine receptors are expressed during early pattern formation in the developing striatum. To test for the functional responsiveness of developing striatal neurons to dopaminergic stimulation, we established an organotypic slice culture of newborn rat striatum. We analyzed the effects of dopamine receptor agonists and of adenylate cyclase and protein kinase activation on striatal neurons by measuring the induction of Fos-like and Fra-like proteins in the cultured striatum. Fos-like and Fra-like proteins were induced in striatal neurons by activation of D1-like dopamine receptors but not by activation of D2-like receptors. The induction of Fos-like protein was mainly in striosomes and a medial compartment next to the ventricular zone, whereas Fra-like protein was induced in the striatal matrix as well. cAMP analogs and forskolin induced widespread expression of both Fos-like and Fra-like proteins. Our findings thus suggest that neurons of developing striosome and matrix compartments not only have different functional coupling of D1-like receptors to adenylate cyclase, but also have distinct maturational programs for dopaminergic regulation of individual transcription factors. Finally, despite evidence that protein kinase was involved in the induction of Fos-like protein, experiments with kinase inhibitors suggested that the induction of Fos-like protein had unusual pharmacological characteristics and raised the possibility that a novel protein kinase A-like molecule may have been involved in the induction. The cultured striatal slice preparation should provide a valuable tool for analyzing the molecular determinants of striatal development and function.