DISTRIBUTION OF SOMATOSTATIN RECEPTOR SUBTYPE-1 MESSENGER-RNA IN THE DEVELOPING CEREBRAL HEMISPHERES OF THE RAT

Somatostatin (SST) is one of the major peptide transmitters in the mam malian central nervous system and also seems to exert specific functio ns during brain development. In contrast to Ligand binding experiments , by which two pharmacologically different binding sites were characte rized, molecular cloning techniques have led to the identification of at least five different receptor subtypes (SSTR1-5), which according t o RNA blot analyses seem to be differentially distributed and regulate d in the developing brain. In order to provide more precise data on th e distribution of SSTR1 during ontogenesis, we have performed an in si tu hybridization analysis, using a 35S-labelled RNA probe, in the deve loping rat cortex between embryonic day (E)12 and adulthood. Within th e cortical plate, expression of SSTR1 gene was first detected in paral lel with the establishment of the deep laminae V/VI at E16, thereby fo llowing the characteristic morphogenetic gradients of cortical plate c onstruction. Thus, with the subsequent addition of cells along the rad ial dimension, e.g. the deposition of the supragranular neurons beyond E18, the hybridization signal spreads as an uniform homogenous band t hrough the entire cortical plate, whereby silver grains reach their pe ak density around birth. Similar developmental gradients were observed along the lateromedial and frontooccipital dimension, whereby SSTR1 t ranscripts were detected near the frontal pole and the lateral cortica l areas roughly 2 days before they appeared in the occipital and media l cortical anlage, respectively. From the initially homogenous distrib ution, two distinct SSTR1 mRNA-positive bands coextensive with laminae V/VI and II/III, respectively, and sparing lamina TV evolved during t he first postnatal week, the grain density of which decreased during f urther postnatal development. Within the hippocampal formation, SSTR1 transcripts were initially observed at E18 in the subicular complex, a nd after birth also extending into the neighboring CA1 region. During the Ist and 2nd postnatal week, silver grains were observed over the p yramidal cell layer of CA2 and CA3 and as a faint supragranular band i n the dentate gyrus. Similar to the isocortex, grain density decreased thereafter. Hypothetically, the pronounced temporospatial regulation of SSTR1 gene expression during brain development can be correlated wi th (1) the establishment and eventual reduction of transient cortical SSTergic neuron populations described for late pregnancy and early pos tnatal development and (2) a receptor subtype exchange during maturati on as evidenced by the late (from postnatal day 7 onward) appearance o f e.g. SSTR3.