Expression of non-N-methyl-D-aspartate glutamate receptor subunits in the olfactory epithelium.

The channel properties of the multimeric ionotropic glutamate receptors can be regulated by their subunit composition. The relationship between 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 heterogeneity. To avoid these difficulties, and to uncover possible novel functions of ionotropic glutamate receptors in sensory neurons, we examined the expression of non-N-methyl-D-aspartate glutamate receptor subunits 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 these neurons, however, terminate and release glutamate in the glomerular region of the olfactory bulb, and may contain presynaptic glutamate receptors. By reverse transcriptase-polymerase chain reaction amplification and RNase protection assays, we showed that a subset of non-N-methyl-D-aspartate receptor subunits is expressed in the olfactory epithelium. The most abundant is KA2, which can form kainate-selective ion channels with GluR5 or GluR6. Messenger RNAs for GluR6, and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate-type (AMPA/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 immunocytochemistry localized KA2 to only the olfactory receptor neurons, and not to any other cell type in the olfactory epithelium. Surprisingly, antibodies against KA2 or GluR5/6/7 primarily stained the olfactory neuron dendritic knobs that are specialized for odorant signalling at the sensory epithelial lumenal surface, and the olfactory neuron axon bundles that project to the olfactory bulb. The presence of a limited subset of non-N-methyl-D-aspartate receptor subunits in the olfactory epithelium, and the localization of a kainate-selective receptor to both the axons and specialized dendritic knobs of olfactory receptor neurons, which receive no known synaptic input, suggest that these non-N-methyl-D-aspartate receptor subtypes may mediate either novel non-synaptic functions in the olfactory neuron dendrites or presynaptic functions in the olfactory nerve terminals or axons. These data also suggest that the olfactory sensory system, possessing a relatively simple anatomical organization and a limited number of glutamate receptor subunits, may be useful for elucidating facets of the complex relationships between subunit composition and physiological function of ionotropic glutamate receptors.

Duke Scholars

Author Dona M. Chikaraishi Neurobiology