ONTOGENY OF THE STRIATAL NEURONS EXPRESSING THE D1 DOPAMINE-RECEPTOR IN HUMANS

We studied D1 dopamine receptor (D1R) gene expression in the human str iatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ( [H-3]SCH 23390) were detected in the striatum from week 12 of fetal li fe. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a patter n similar to D1R mRNA. D1R-IR was essentially present in striosomal ce ll bodies and neuropil, whereas only a few cell bodies were detected i n the matrix. From week 20 of fetal life, D1R gene expression develope d in the matrix neurons as well, thus leading to an even D1R mRNA expr ession throughout striosomes and matrix compartments at birth. Compara tive analysis of the expression of D1R and dynorphin mRNA show the sam e developmental patchy pattern up to week 26. Indeed, neurons expressi ng the D1R gene contain dynorphin mRNA; in contrast, they do not expre ss the preproenkephalin A gene. At birth, the pattern of D1R mRNA expr ession level was sharply different from that of dynorphin (DYN) gene e xpression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. Th ese results demonstrate that, during human ontogeny, functional D1 rec eptors are expressed as early as week. 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA con tent. Toward the end of fetal life, there is a dissociation between D1 R and DYN expression levels, suggesting that neuroanatomical or neuroc hemical modifications occur at this period, which may contribute to th e regulation of the tone of the striatal D1R and DYN gene with topolog ical specificity. (C) 1996 Wiley-Liss, Inc.