Dopaminergic control of gene transcription during striatal ontogeny: c-fos induction by D1 receptor activation in the...

During striatal development, dopamine afferents initially reach the striosomal compartment, and this early dopamine innervation is thought to influence, through the D1 receptors first expressed in the developing patches, the phenotype of target striatal cells. Dopaminergic control of gene expression during ontogeny could be mediated by transcription factors such as c-fos, whose expression is regulated by synaptic signals. However, in the striatum of intact adult animals, D1 dopamine agonists fail to induce c-fos expression. The c-fos response to D1 receptor activation in adults requires a previous sensitization of dopaminergic receptors by chronic treatment with reserpine or by lesion of the nigro-striatal pathway. In this work, we investigated through in situ hybridization the ability of striatal cells to express c-fos messenger RNA (mRNA) in response to the D1 agonist SKF 38393 (4 to 8 mg/kg) in developing mice. During a transient postnatal period, c-fos expression in a patchy distribution was induced by D1 receptor activation: only a faint response was detected on postnatal day 1, but islands of strong hybridization signals for c-fos mRNA in response to the D1 agonist were observed at postnatal day 3, with a progressive decrease in intensity from day 6 to day 15. The distribution of this transient c-fos response corresponded to the early striosomal compartment since it matched with the regions of intense mu-opioid and dopamine-D1 receptor binding, as assessed by autoradiography performed on adjacent sections. By day 21, as in adult animals, no more c-fos response to D1 agonists was observed, except in the most caudal division of the striatum. Strong expression, which persisted into adulthood, was detected in this region from the third postnatal day. This induction of striatal c-fos expression by D1 agonists during early postnatal development is indicative of an enhanced sensitivity of D1 receptors or of D1-associated transduction pathways compared to the adult pattern, and suggests a possible role for dopamine-controlled c-fos gene expression in the development of target striatal neurons during this critical period.