DISTRIBUTION OF GLUTAMATERGIC RECEPTORS AND GAD MESSENGER-RNA-CONTAINING NEURONS IN THE VESTIBULAR NUCLEI OF NORMAL AND HEMILABYRINTHECTOMIZED RATS

Vestibular compensation is an attractive model for investigations of c ellular mechanisms underlying post-lesional plasticity in the adult ce ntral nervous system. Immediately after hemilabyrinthectomy, the spont aneous activity in the deafferented second-order vestibular neurons fa lls to zero, resulting in a strong asymmetry between the resting disch arge of the vestibular complexes on the lesioned and intact sides. Thi s asymmetry most probably causes the static and dynamic vestibular def icits observed in the acute stage. After similar to 50 h, the deaffere nted vestibular neurons recover a quasi-normal resting activity which is thought to be the key of the compensation of the static vestibular syndromes. However, the molecular mechanisms underlying this recovery are unknown. In this study, we investigate possible changes in the dis tribution of glutamatergic N-methyl-D-aspartate (NMDA) and glutamate m etabotropic receptors and of glutamate decarboxylase 67k (GAD 67k) mRN As in the deafferented vestibular neurons induced by the labyrinthine lesion. Specific radio-active oligonucleotides were used to probe sect ions of rat vestibular nuclei according to in situ hybridization metho ds. Animals were killed at different times (5 h, 3 days and 3 weeks) f ollowing the lesion. Signal was detected by means of film or emulsion autoradiography. In the normal animals, several brainstem regions incl uding the medial, lateral, inferior and superior vestibular nuclei wer e densely labelled by the antisense oligonucleotide NMDAR1 probe. Howe ver, the vestibular nuclei were not labelled by the glutamate metabotr opic oligonucleotide antisense probe (mGluR 1). The GAD 67k antisense oligonucleotide probe labelled numerous small- to medium-sized central vestibular neurons but not the larger cell bodies in the lateral vest ibular nucleus. This agrees with previous studies. In the hemilabyrint hectomized rats, no asymmetry could be detected, at either the autorad iographic or cellular levels, between the two medial vestibular nuclei whatever the probe used and whatever the delay following the lesion. However, for the NMDAR1 probe, the mean density of silver grains in bo th the deafferented and intact medial vestibular neurons was 20% lower 5 h after the lesion. Three days and 3 weeks later, the intensity of labelling over all cells was the same as in the control group. Further studies are necessary to confirm the relatively weak modification of the NMDAR1 mRNAs expression and to exclude a change of GAD 65 and of o ther NMDA subunit mRNAs during the vestibular compensation process.