- • Perirhinal cortex (Prh) is critically involved in visual recognition memory and synaptic plasticity.
- • Nitric oxide and endocannabinoids (eCBs) have been shown to act as retrograde messengers in synaptic plasticity in several brain areas, but no study has yet investigated their role in synaptic plasticity in Prh.
- • Evidence is still lacking of a retrograde messenger involved in synaptic plasticity in Prh.
- • In this study, we show that NO is involved in long-term depression (LTD) but not in long-term potentiation (LTP). Conversely, eCBs are involved in LTP but not in LTD. Crucially, inhibiition of NO signalling prevents visual recognition memory acquisition, whilst inhibition of eCB signalling does not affect recognition memory.
- • These results suggest that LTD but not LTP is a neuronal correlate of visual recognition memory.
Abstract Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory.