Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus

The excitatory amino acid neurotransmitter glutamate participates in the co ntrol of most (and possibly all) neuroendocrine systems in the hypothalamus . This control is exerted by binding to two classes of membrane receptors, the ionotropic and metabotropic receptor families, which differ in their st ructure and mechanisms of signal transduction. To gain a better understandi ng about the precise sites of action of glutamate and the subunit compositi ons of the receptors involved in the glutamatergic neurotransmission in the hypothalamus and septum, in situ hybridization was used with S-35-labeled cRNA probes for the different ionotropic receptor subunits, including gluta mate receptor subunits 1-4 (GluR1-GluR4), kainate-2, GluR5-GluR7, N-methyl- D-aspartate (NMDA) receptor 1 (NMDAR1), and NMDAR2A-NMDAR2D. The results sh owed that subunits of alpha -amino-3-hydroxy-5-methyl-4-isoxazole-propionat e-preferring, kainate-preferring, and NMDA-preferring receptor subunits are distributed widely but heterogeneously and that the GluR1, GluR2, kainate- 2, NMDAR1, NMDAR2A, and NMDAR2B subunits are the most abundant in the hypot halamus. Thus, GluR1 subunit mRNA was prominent in the lateral septum, preo ptic area, mediobasal hypothalamus, and tuberomammillary nucleus, whereas k ainate-2 subunit mRNA was abundant in the medial septum-diagonal band, medi an and anteroventral preoptic nuclei, and supraoptic nuclei as well as the magnocellular portion of the posterior paraventricular nucleus. Regions tha t contained the highest levels of NMDAR1 subunit mRNA included the septum, the median preoptic nucleus, the anteroventral periventricular nucleus, and the supraoptic and suprachiasmatic nuclei as well as the arcuate nucleus. Together, the extensive distribution of the different GluR subunit mRNAs st rengthen the view that glutamate is a major excitatory neurotransmitter in the hypothalamus. The overlap in the distribution of the various subunit mR NAs suggests that many neurons can express GluR channels that belong to dif ferent families, which would allow a differential regulation of the target neurons by glutamate. (C) 2001 Wiley-Liss, Inc.