RORα Coordinates Thalamic and Cortical Maturation to Instruct Barrel Cortex Development.

The retinoic acid-related orphan receptor alpha (RORα) is well-known for its role in cerebellar development and maturation as revealed in staggerer mice. However, its potential involvement in the development of other brain regions has hardly been assessed. Here, we describe a new role of RORα in the development of primary somatosensory maps. Staggerer mice showed a complete disruption of barrels in the somatosensory cortex and of barreloids in the thalamus. This phenotype results from a severe reduction of thalamocortical axon (TCA) branching and a defective maturation of layer IV cortical neurons during postnatal development. Conditional deletion of RORα was conducted in the thalamus or the cortex to determine the specific contribution of RORα in each of these structures to these phenotypes. This showed that RORα is cell-autonomously required in the thalamus for the organization of TCAs into periphery-related clusters and in the somatosensory cortex for the dendritic maturation of layer IV neurons. Microarray analyses revealed that Sema7a, Neph, and Adcy8 are RORα regulated genes that could be implicated in TCA and cortical maturation. Overall, our study outlines a new role of RORα for the coordinated maturation of the somatosensory thalamus and cortex during the assembly of columnar barrel structures.

In vivo 1H MRS study in microlitre voxels in the hippocampus of a mouse model of Down syndrome at 11.7 T.

In this article, we report in vivo (1)H MRS performed in 1.8-µL voxels in a mouse model of Down syndrome (DS). To characterise the excitation-inhibition imbalance observed in DS, metabolite concentrations in the hippocampi of adult Ts65Dn mice, which recapitulate features of DS, were compared with those of their euploid littermates at a voxel 42-fold smaller than in a previously published study. Quantification of the metabolites was performed using a linear combination model. We detected 16 metabolites in the right and left hippocampi. Principal component analysis revealed that the absolute concentrations of the 16 detected metabolites could differentiate between Ts65Dn and euploid hippocampi. Although measurements in the left and right hippocampi were highly correlated, the concentration of individual metabolites was sometimes significantly different in the left and right structures. Thus, bilateral values from Ts65Dn and euploid mice were further compared with Hotelling's test. The level of glutamine was found to be significantly lower, whereas myo-inositol was significantly higher, in the hippocampi of Ts65Dn relative to euploid mice. However, γ-aminobutyric acid (GABA) and glutamate levels remained similar between the groups. Thus, the excitation-inhibition imbalance described in DS does not appear to be related to a radical change in the levels of either GABA or glutamate in the hippocampus. In conclusion, microliter MRS appears to be a valuable tool to detect changes associated with DS, which may be useful in investigating whether differences can be rescued after pharmacological treatments or supplementation with glutamine.