NR2B-containing NMDA receptors are required for LTD in the perirhinal cortex in vitro P.V.Massey, B.E.Johnson, M.W.Brown, E. Molnar, Z.I.Bashir. MRC Centre for Synaptic Plasticity, Dept. of Anatomy, University of Bristol, BS8 1TD, UK.

Print abstract Search PubMed for: Massey PV Johnson BE Brown MW Molnar E Bashir ZI

N-methyl-D-aspartate (NMDA) receptors are composed of an essential NR1 subunit together with one or more NR2 (A-D) subunits. NMDA receptor activation is a critical step required for the induction of long-term synaptic depression (LTD) in the nervous system. Induction of NMDA receptor-dependent LTD in vitro using standard low frequency stimulation (LFS; 900 stimuli, 1 Hz) is developmentally down-regulated in numerous brain areas (Kemp & Bashir., 2001) including adult rat perirhinal cortex (Ziakopoulos et al., 1999). The aim of the present study was to investigate the mechanisms potentially responsible for this down-regulation of LTD in the perirhinal cortex.

Slices of perirhinal cortex were prepared from adult (150-270g, 7 to 12 weeks) or juvenile (14-day) rats. Animals were anasthetized with halothane and decapitated in accordance with the U.K Animals (Scientific Procedures) Act 1986. Experiments were carried out using standard extracellular recording techniques. Excitatory postsynaptic Field potentials (fEPSPs) were recorded in cortical layers II/III of rat perirhinal cortex either side of the rhinal sulcus in response to stimuli (each electrode 0.033 Hz) delivered to entorhinal and temporal sides. The peak amplitude of the fEPSPs were plotted on-line and subsequently analysed off-line (Anderson & Collingridge., 2001).

LFS was delivered to induce LTD. Compared to the pre-LFS baseline, LTD was defined as a decrease in the magnitude of evoked potential of > 10% at 30 min after LFS and for the remainder of the recording.

In juvenile (14-day) perirhinal cortex, delivery of LFS alone resulted in homosynaptic LTD, whereas this procedure was ineffective in adult slices. However, in adult slices LTD could be induced either by bath application of NMDA (20µM) or by delivery of LFS in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (t-PDC; 300µM). In each case LTD was blocked by the NMDA receptor antagonist AP5.

Ro-25,6981 (3µM), a potent NR2B-selective antagonist, blocked LFS-induced LTD both in juvenile slices, and that achieved in adult cortex with LFS in the presence of t-PDC or by application of NMDA.

These results suggest that developmental down-regulation of LTD in the perirhinal cortex results from a decrease in the activation of NR2B-containing receptors by synaptically released glutamate.

Supported by MRC, Wellcome and BBSRC.

Anderson & Collingridge (2001) J Neurosci Meth 108: 71-83.
Kemp & Bashir (2001) Prog Neurobiol 65: 339-65.
Ziakopoulos et al. (1999) Neuroscience 92: 459-72.