A primary function of the perirhinal cortex is in the process of recognition memory, particularly familiarity discrimination. Evidence that there is a decremental response in perirhinal neurones upon exposure to familiar objects (Brown & Xiang, 1998), has led to the proposal that long term depression (LTD) at perirhinal synapses could be a plastic mechanism underlying recognition memory (Brown & Bashir 2002). The role of AMPA receptor recycling within recognition memory and LTD expression in the perirhinal cortex has yet to be investigated. The trafficking protein AP2 acts as an adapter for clathrin-mediated endocytosis of AMPA receptors. It has an overlapping binding site on the C-terminus of the GluR2 subunit with NSF, an ATPase associated with maintaining AMPA receptors at the synapse (Lee et al. 2002). In this report we have investigated the role of GluR2 and its interactions with AP2 and NSF upon LTD in the perirhinal cortex. Perirhinal cortex slices were prepared from humanely killed adult male DA rats. Whole-cell voltage clamp recordings were made from layer II/III neurones. Low-frequency stimulation (LFS; 200 stimuli, 1Hz) combined with depolarisation to -40mV resulted in LTD (43 ± 5% of baseline, n=7). This form of LTD is NMDAR-dependent since bath application of 50μM AP5 (NMDAR antagonist) inhibited LTD induction (91 ± 5%, n=6). Antagonism of GluR5 and mGluR receptors with 5μM UBP302 and 100μM LY341495, respectively, had no effect upon LTD induction (46 ± 6%, n=3; 44 ± 11%, n=3). Specific inhibitory polypeptides of the AP2- or the NSF-GluR2 interaction were introduced, via the intracellular whole-cell solution. In line with results from the hippocampus, LTD expression was blocked by the AP2 specific inhibitory peptide pep-ΔA849-Q853 (94 ± 5%, n=6) but was unaffected by pep-R845A (44 ± 5%, n=5) (Lee et al. 2002). Pep2m, which inhibits NSF and AP2, also blocked LTD expression (95 ± 1%, n=3). However, the specific NSF inhibitory peptide pep-R845A and pep2m, which cause run-down of hippocampal baseline EPSCs, had no effect on baseline transmission in perirhinal neurones. These results suggest that AP2 is vital for LTD expression but that NSF may potentially have a different role in AMPA receptor trafficking in the perirhinal cortex, compared with the hippocampus.