Perirhinal cortex is association cortex that has been shown to be critically involved in visual recognition memory, and loss of recognition memory is a major symptom of the amnesic syndrome and early Alzheimer’s disease (Brown & Aggleton, 2001). There is good evidence that the familiarity discrimination component of recognition memory depends on reductions in responses of perirhinal neurones (Warburton et al. 2003). Therefore, it is thought that a potential cellular mechanism of encoding this form of memory is through synaptic plasticity, such as long-term depression (LTD) (Brown & Bashir, 2002; Warburton et al. 2003). Mechanisms of synaptic plasticity, such as LTP and LTD, are thought to underlie development of the CNS and learning and memory. Synaptic plasticity is known to be developmentally regulated in many brain regions and the changes in mechanisms that occur during development are a matter of intense investigation (Kemp & Bashir 2001; Philpot et al. 2001). In the present study, we demonstrate that during development of the perirhinal cortex LTD switches from being metabotropic glutamate (mGlu) receptor-dependent to being muscarinic acetylcholine receptor-dependent. Importantly, this switch occurs as a consequence of visual experience and suggests that changing physiological functions require or produce different forms of synaptic plasticity. Slices of perirhinal cortex were prepared from neonatal (7–12 day old) and adult (28–35 day old) Wistar rats. All efforts were made to minimize the numbers of animals used. Animals were humanely killed. Either standard whole-cell or field recordings were used during this study. Data for any set of experiments were only analysed from one slice per rat (n). Data pooled across slices are expressed as the mean ± SEM and significance (P〈0.05). 5 Hz stimulation delivered to neonatal (P7–12) perirhinal cortex slices resulted in robust NMDA receptor-independent homosynaptic LTD (29 ± 7%, n=7). To minimise any possible confounding contribution of NMDA receptor activation under different conditions, all subsequent experiments were carried out in the presence of 50μM AP5. In many other studies it has been shown that LTD that is NMDA receptor-independent is mGluR-dependent (Kemp & Bashir. 2001). In keeping with this, the mGluR5 receptor antagonist MPEP (10μM), blocked LTD in a reversible manner in P7–12 perirhinal cortex (5 ± 1% depression in MPEP; 18 ± 3% depression after washout of MPEP, n=7). In contrast, however, neither group II nor group III mGlu receptor antagonists (200μM EGLU and 100nM CPPG, respectively) had any effect on LTD (25 ± 1%, n=5, EGLU; 22 ± 2%, n=4, CPPG). 5 Hz stimulation also resulted in NMDA receptor-independent LTD in adult (P28–35) perirhinal cortex (18 ± 1%, n=5). However, in contrast to LTD in P7–12 animals, LTD was not mGlu5 receptor-dependent; the mGlu5 antagonist MPEP had no effect on 5 Hz-LTD in adult cortex (18 ± 2% LTD, n=6). Therefore, LTD in the adult cortex relies on cellular mechanisms different to LTD in P7–12 cortex. In the present study we find that inhibition of muscarinic receptors blocked 5 Hz-LTD in P28–35 perirhinal cortex (2 ± 3% in 20μM scopolamine; n=6). In contrast to these results, the muscarinic receptor antagonist scopolamine did not prevent the induction of LTD in P7-12 perirhinal cortex (32 ± 5% in scopolamine, n=6). Since eye opening occurs at about postnatal days 13-15 it is possible that the visual information received by perirhinal cortex at this age is involved in the developmental switch in LTD mechanisms that we have observed. To examine whether the change from mGlu to muscarinic LTD arises as a consequence of visual experience, LTD was examined in dark-reared P28-35 rats. The mGlu5 antagonist MPEP prevented the induction of LTD in dark-reared P28-35 rats (2 ± 5% in MPEP and 25 ± 6% after washout of MPEP, n=5). In contrast, the inhibition of muscarinic receptors had no effect on LTD in dark-reared P28-35 rats (27 ± 5% depression, n=5). The present results show that experience-dependent visual activity is an important factor in the modification of LTD induction mechanisms in downstream association perirhinal cortex. It is still a matter of speculation how visual experience triggers the changes in LTD mechanisms but it is likely that appropriate coordinated visual activity into perirhinal cortex somehow up-regulates muscarinic receptor expression or function whilst down-regulating mGluR expression or function.