KAINATE RECEPTOR GENE-EXPRESSION IN THE DEVELOPING RAT-BRAIN

Kainate-preferring receptors are a subclass of ionotropic glutamate re ceptors that might play a role in brain development. The expression of the five known genes encoding kainate receptor subunits (GluR-5, -6, -7, KA-1, and KA-2) was studied by in situ hybridization during pre- a nd postnatal development of the rat brain. We compared the combined ex pression patterns of these genes with autoradiography using H-3-kainat e in the developing brain from embryonic day 12 (E12) through to adult . Although mRNAs for the receptor subunits (except KA-1) can be detect ed at stage E12, H-3- kainic acid binding (as an index of receptor pro tein) is not found at this stage. However, by E14 high-affinity kainat e sites are found throughout the gray matter, but particularly in spin al cord, primordial cerebellum, and ventral forebrain structures. All genes undergo a peak in their expression in the late embryonic/early p ostnatal period. GluR-5 expression during development shows the most i nteresting features because the changes are qualitative. The GluR-5 ge ne shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in t he stratum oriens, in the septum, and in the thalamus. GluR-6 shows a prenatal expression peak in the cingulate gyrus of the neocortex. KA-1 transcripts appear with the development of the hippocampus and remain largely confined to discrete areas such as the CA3 region, the dentat e gyrus, and subiculum. KA-2 transcripts are found throughout the CNS from as early as E12 and remain constant until adulthood. The GluR-5 a nd GluR-6 genes are coexpressed in multiple peripheral ganglia (e.g., cranial nerve ganglia, dorsal root ganglia, and mural ganglia) at E14.