The perirhinal cortex is implicated in the discrimination of novel and familiar stimuli. The firing rate of perirhinal cortical neurones decreases as a novel object becomes familiar after repeated presentation. Whilst the mechanism underlying the decrease in firing rate is not fully understood, there is growing evidence that a reduction in perirhinal synaptic efficacy may be involved. Rat perirhinal synapses have recently been shown to support a robust form of activity-dependent long-term depression (LTD) (Cho et al. 2000). We report here, that a similar form of LTD is also a feature of the mouse perirhinal cortex.

Coronal cortical slices (400 µm thick) were prepared from mice (B6xCBA) aged 1-2 months, killed humanely by cervical dislocation. Slices, containing the perirhinal cortex, were maintained at 25°C in an interface chamber. Recording microelectrodes (2-5 MV)were placed in layer II/III of the perirhinal cortex and field EPSPs evoked by monopolar stimulation of the superficial layer. Short-term plasticity (paired-pulse) was examined. LTD was induced using a low-frequency stimulation (LFS) protocol (900 shocks at 1 Hz) and data are expressed as mean percent change in EPSP amplitude ± S.E.M., measured 1 h post conditioning (P values obtained using an unpaired t test).

Paired-pulse stimulation (interpulse interval, 20-2000 ms) produced paired-pulse profiles that favoured depression of the second response, a result which is consistent with the predominance of paired-pulse depression seen at rat perirhinal synapses. LFS of superficial synapses induced homosynaptic LTD -11.7 ± 3.2 %, n = 19).

In the rat, perirhinal LTD has been shown to be dependent on both the activation of NMDA receptors and metabotropic glutamate (mGlu) receptors. In agreement, LTD at mouse perirhinal synapses was blocked by group I (500 µM AIDA) and group II (1 µM LY341495) mGlu receptor antagonists, 2.6 ± 1.7 % (n = 10, P < 0.001) and -1.1 ± 2.7 % (n = 10, P < 0.02) respectively, but was unaffected by a group III antagonist (10 µM CPPG), -11.2 ± 3.1 % (n = 6, P > 0.5). In contrast, application of the NMDA receptor antagonist, 50 µM D-AP5, failed to block the induction of LTD at mouse perirhinal synapses, -10.3 ± 5.9 % (n = 10; P > 0.5).

We also examined the action of these drugs on perirhinal paired-pulse depression. Interestingly, the drugs that blocked the induction of LTD also reduced paired-pulse depression whereas those drugs that had little effect on LTD induction did not markedly alter the paired-pulse profile.

The data presented here suggest that LTD is a feature of both rat and mouse perirhinal cortices. However, in the mouse, NMDA receptors do not appear to be involved in the induction of LTD at superficial synapses.

The authors thank S. Walters, D. Sadler and K. Evans.