TRPV1 channels as putative targets in the cannabinoid-mediated synaptic activity of hippocampal neurons

Endocannabinoids (eCBs) play a critical part in pathophysiological conditions rooted on neuronal excitability such as epilepsy. eCBs seem to be involved in neuroprotection, putatively acting on the cannabinoid receptor type 1 (CB1r), but also on Transient Receptor Potential Vanilloid type 1 channels (TRPV1). Indeed, CB1r and TRPV1 are involved in the transduction of stimuli at synaptic level, though exact molecular mechanisms are far from being unveiled. Thus, we aimed to investigate the role of CB1r/TRPV1 interplay in the rat hippocampal neurotransmission by whole-cell patch clamp technique to evaluate excitatory bioelectric activity in the CA1. We pharmacologically manipulated this pathway with anandamide (AEA), CB1r and TRPV1 agonist, capsaicin (CAP), TRPV1 agonist and capsazepine (CPZ), TRPV1 antagonist. Our data show that drug application significantly modifies synaptic activity by influencing action potentials parameters and mini excitatory post-synaptic currents (mEPSC). In particular, CPZ increased mEPSC amplitude, whereas CAP reduced it. As for the implication of presynaptic terminal, our results revealed that CPZ decreased mEPSC frequency and CAP increased it, also modifying in accordance the cumulative probability of inter-event intervals. Interestingly, AEA co-administration with CPZ reverts its effects, whilst CAP activity is potentiated in co-administration with AEA. Our preliminary results support the hypothesis that CB1r/TRPV1 could modulate excitatory neurotransmission ultimately improving synaptic efficiency at various levels. In this light, TRPV1 emerge as possible targets in the cannabinoid neuroprotective modulation of hippocampal bioelectric activity.