Presynaptic mechanisms of endocannabinoid-mediated long-term depression in the hippocampus

Endogenous cannabinoids (eCBs) mobilized from postsynaptic cells activate presynaptic cannabinoid receptors and thereby inhibit synaptic transmitter release. The inhibition can be either brief (seconds) or longlasting (minutes to hours). Recent studies provide insight into the presynaptic mechanisms responsible for long-lasting, eCB-mediated long-term depression. Among these, the proteins PKA and RIM1α appear to be crucial, although other possibilities are emerging.