title: Increased expression, but not postsynaptic localisation, of ionotropic glutamate receptors during the late-phase of long-term potentiation in the dentate gyrus in vivo.
abstract: Long-term potentiation (LTP) is extensively studied as a cellular mechanism of information storage in the brain. The induction and early expression mechanisms of LTP depend on activation and rapid modulation of ionotropic glutamate receptors. However, the mechanisms that underlie maintenance of LTP over the course of days or longer are poorly understood. Here, we have investigated the overall expression of AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively), as well as their levels at the synaptic surface membrane and in the postsynaptic density (PSD), in the dentate gyrus at 48h following the induction of LTP at perforant path synapses in awake rats. We found a high-frequency stimulation-dependent increase in the overall levels of AMPAR subunits GluA1 and GluA2, but not GluA3 in the dentate gyrus. The increases in GluA1 and GluA2 levels were partially NMDAR-dependent, but were not found in biochemically isolated synaptic surface membrane or PSD fractions. In contrast, we found that the core NMDAR subunit, GluN1, increased in the synaptic surface-membrane fraction but it also was not targeted to the PSD. The GluA1 and GluA2 expression and the surface localisation of GluN1 returned to baseline levels by 2 weeks post-LTP induction. These data suggest that the late-phase LTP is not mediated by an overt increase in the AMPAR content of perforant path synapses. The increase in surface expression NMDARs may influence thresholds for future plasticity events.
authors.affiliation: Department of Anatomy and Structural Biology, Brain Health and Repair Research Centre, Otago School of Medical Sciences, P.O. Box 913, Dunedin, New Zealand. jeremy.kennard@anatomy.otago.ac.nz
authors.forename: Jeremy T T
authors.initials: JT
authors.lastname: Kennard
authors.forename: Diane
authors.initials: D
authors.lastname: Guévremont
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mason-Parker
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Williams