EXPRESSION OF NON-N-METHYL-D-ASPARTATE GLUTAMATE-RECEPTOR SUBUNITS INTHE OLFACTORY EPITHELIUM

The channel properties of the multimeric ionotropic glutamate receptor s can be regulated by their subunit composition. The relationship betw een the structure and physiological functions of glutamate receptors, however, is difficult to study in the CNS because of the large number of these subunits, their widespread distribution, and neuronal heterog eneity. To avoid these difficulties, and to uncover possible novel fun ctions of ionotropic glutamate receptors in sensory neurons, we examin ed the expression of non-N-methyl-D-aspartate glutamate receptor subun its in a simple neuronal system: the olfactory epithelium. It contains only one neuronal type, the olfactory receptor neuron, that receives no synaptic innervation within the epithelium and therefore should not require conventional postsynaptic glutamate receptors. The axons of t hese neurons, however, terminate and release glutamate in the glomerul ar region of the olfactory bulb, and may contain presynaptic glutamate receptors. By reverse transcriptase-polymerase chain reaction amplifi cation and RNase protection assays, we showed that a subset of non-N-m ethyl-D-aspartate receptor subunits is expressed in the olfactory epit helium. The most abundant is KA2. which can form kainate-selective ion channels with GluR5 or GluR6. Messenger RNAs for GluR6, and for the a lpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate-type (AMP A/KA) GluR2 and GLuR3 subunits, are also present, but at levels lower than that of KA2 by an order of magnitude. In situ hybridization and i mmunocytochemistry localized KA2 to only the olfactory receptor neuron s. and not to any other cell type in the olfactory epithelium. Surpris ingly, antibodies against KA2 or GluR5/6/7 primarily stained the olfac tory neuron dendritic knobs that are specialized for odorant signallin g at the sensory epithelial lumenal surface, and the olfactory neuron axon bundles that project to the olfactory bulb. The presence of a lim ited subset of non-N-methyl-D-aspartate receptor subunits in the olfac tory epithelium, and the localization of a kainate-selective receptor to both the axons and specialized dendritic knobs of olfactory recepto r neurons, which receive no known synaptic input, suggest that these n on-N-methyl-D-aspartate receptor subtypes may mediate either novel non -synaptic functions in the olfactory neuron dendrites or presynaptic f unctions in the olfactory nerve terminals or axons. These data also su ggest that the olfactory sensory system, possessing a relatively simpl e anatomical organization and a limited number of glutamate receptor s ubunits, may be useful for elucidating facets of the complex relations hips between subunit composition and physiological function of ionotro pic glutamate receptors. (C) 1997 IBRO. Published by Elsevier Science Ltd.