Spatio-temporal heterogeneity and cell-specificity of long-term potentiation-induced mRNA expression in the dentate gyrus in vivo

Abstract

Gene expression in neurones can vary in response to neuronal activation. In this study, to analyse the spatio-temporal dynamics of the transcriptional response of three genes following the induction of long-term potentiation within the entire dentate gyrus in vivo, two new complementary approaches based on in situ hybridisation were developed: three-dimensional reconstruction of the pattern of mRNA expression within the entire dentate gyrus; and radioactive co-detection of two mRNA species allowing quantification of two different mRNAs in the same brain section. Zif268, Homer and syntaxin 1B genes were studied, and their regulated expression was examined three times after the induction of long-term potentiation. Constitutive expression of each gene under control conditions was homogeneous, but the spatial distribution of mRNA was heterogeneous along the rostro-caudal axis of the dentate gyrus following the induction of long-term potentiation, and different for each gene. In addition, the intensity of each gene-specific pattern of expression varied over time following the induction of long-term potentiation. Our results reveal that long-term potentiation differentially modulates the expression of mRNA species in cells of the dentate gyrus depending on their position along the rostro-caudal axis, on the gene and on time. We suggest that there are several molecular mechanisms of long-term potentiation, differing from one cluster of cells of the dentate gyrus to another, or that the different signaling pathways involved in long-term potentiation are used with varying efficiencies by different cells.