Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers that are involved in synaptic plasticity as well as in learning and memory. NO mainly exerts its functions through soluble guanylate cyclase (sGC) activation. Activity-dependent release of eCBs in the central nervous system leads to the activation of the Gi/o-coupled cannabinoid receptor 1 (CB1) at both excitatory and inhibitory synapses.

The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in recognition memory. Long-term depression (LTD) is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission plays a critical role in both visual recognition memory and LTD in Prh. The aim of the present research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh.

Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti (p21-35) rats. LTD was induced with a single train of 3000 pulses at 5 Hz, or via bath application of carbachol (Cch; 50 mM) for 10 min. Long-term potentiation (LTP) was induced by theta-burst stimulation (TBS).

We found that 5Hz-LTD and Cch-LTD induction rely on the activation of the NOS/sGC pathway but not on CB1. By contrast, TBS-LTP was shown to require CB1 but not NOS activation. These results demonstrate that distinct retrograde signalling underlies different forms of synaptic plasticity in the perirhinal cortex.