The abundant expression of RGS (regulator of G-protein signalling) proteins in neurons, together with their modulatory function on G-protein-dependent neurotransmission, provides the basis for cellular adaptation to sensory inputs. To identify the molecular mechanism involved in the sensory experience-induced neural development, we performed a systematic survey of the localization of mRNAs encoding three subtypes of the RGSs (RGS2, RGS4 and RGS7) in developing rat brains by in situ hybridization through postnatal day 2 (P2), P10 and P18 to adult. The most dramatic changes of expression patterns were observed in the discrete neuronal cell layers of the cerebral neocortex (for RGS2 and 4), the hippocampus (for RGS2, 4 and 7), the thalamus (for RGS4) and the cerebellum (for RGS2 and 7). In the neocortex, RGS2 mRNA was enriched in the superficial cortical plate at P2, in contrast to RGS4, which was enriched in more mature neurons of the deeper layer V and VI. In the hippocampus, the neuronal cell layer-specific expression pattern of RGS2 developed from P2 to P18. RGS4 expression was temporarily confined to the CA pyramidal cell layer and not detectable in the dentate gyrus at P10 and P18. Similarly, a high level of expression of RGS7 was observed in the CA area, but not in the dentate gyrus at P2 and P10. In the cerebellum, the maturation of laminar expression patterns for the three RGSs correlated with neuronal maturation and synaptogenesis at P18. The most characteristic temporal pattern among the three RGSs was observed for RGS4 mRNA, which was highly enriched in the thalamocortical regions. The peaks of RGS4 expression were seen in the following regions with distinct onset and duration: the neocortex (from P2 onward), the hippocampus (P10 and P18) and the thalamus (from P18 onward). The divergent temporal and spatial expression of RGS subtypes and their dynamic control in the cortex, the hippocampus and the thalamus suggest that the RGS family could play multiple distinct roles in experience-dependent brain development.