ALTERATIONS IN THE EXPRESSION OF SPECIFIC GLUTAMATE-RECEPTOR SUBUNITSFOLLOWING HIPPOCAMPAL LTP IN-VIVO

Quantitative in situ hybridization revealed that following the inducti on of hippocampal long-term potentiation (LTP) in the dentate gyrus of freely moving rats, specific increases in the expression of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor and mGluR1c, a sho rt splice variant of the metabotropic glutamate receptors that are lin ked intracellularly to phospholipase C (PLC) and protein kinase C (PKC ), were seen in the postsynaptic dentate granule cells. There were no changes in the expression of NR2A; NR2C and NR2D NMDA receptor subunit s; or mGluR1a, mGluR1b, mGluR5a, and mGluR5b PLC-associated metabotrop ic receptors. The elevations in NR2B and mGluR1c mRNA were delayed, oc curring days after LTP induction. NR2B expression was enhanced signifi cantly by 48 hr after LTP but was starting to decrease toward basal le vels by 96 hr. The transient increase in the expression of NR2B mirror ed the increase in the expression of PKC-sensitive isoforms of the NR1 subunits of the NMDA receptor we observed previously (Thomas et al. 1 994a). The increase in mGluR1c expression was more persistent, showing a significant increase 96 hr after LTP. This study demonstrates that not only are there changes Ln the expression of individual glutamate r eceptor subunits but the increases in their expression occur days afte r the induction of LTP and may reflect so-called late-onset genes that may be important for the maintenance of LTP.