Quantitative changes in gene expression of glutamate receptor subunits/subtypes in the vestibular nucleus, inferior olive and flocculus before and following unilateral labyrinthectomy in the rat: real-time quantitative PCR method

Spontaneous recovery from the oculomotor and postural symptoms of unilatera l labyrinthectomy (UL) is known as vestibular compensation, which is a usef ul model for investigation of the mechanisms of lesion-induced CNS plastici ty. In the present study, to elucidate the molecular biological basis of ve stibular compensation, we investigated changes in the mRNA expression of gl utamate receptor subunit/subtypes in the rat central vestibular system, inc luding the vestibular nucleus complex (VNC), inferior olive (IO), and cereb ellar flocculus following UL, using a real-time quantitative polymerase cha in reaction (PCR) method. In normal control animals, regional differences i n the expression of several glutamate receptor subunit/subtypes, e.g., NR1 and NR2A subunits of the N-methyl-D-aspartic acid (NMDA) receptor, GluR2 an d KA2 subtypes of non-NMDA receptors, and mGluR1 and mCluR7 metabotropic gl utamate receptors, were consistent with previous results from studies using in situ hybridization histochemistry, suggesting that the real-time quanti tative PCR method was a reliable procedure for evaluation of changes in mRN A expression. In the vestibular nucleus complex, NR2A, GluR2 and mGluR7 mRN A were ipsilaterally downregulated by 6 h following UL (P<0.05, P<0.05 and P<0.01, respectively). In the inferior olive, no changes in gene expression were observed. In the ipsilateral flocculus, KA2 mRNA expression was incre ased by 50 h post-UL (P<0.05). However, in the contralateral flocculus, mGl uR1 mRNA was downregulated by 6 h post-UL (P<0.005). Both the increase in K A2 mRNA expression in the ipsilateral flocculus and the decrease in mGluR1 mRNA expression in the contralateral flocculus may have had the effect of r educing Purkinje cell inhibition of ipsilateral VNC neurons, thereby contri buting to the rebalancing of spontaneous resting activity between the ipsil ateral and contralateral VNCs. It is suggested that such changes in the act ivities of the floccular-VNC pathways may be important to the vestibular co mpensation process.