Abstract
Recent studies have revealed that endocannabinoids (eCB) are released from postsynaptic neurons and suppress transmitter release in various regions of the CNS. In this presentation, we introduce our recent studies on the eCB-mediated retrograde suppression and its regulation by Ca2+ in hippocampal neurons. We used highly cannabinoid-sensitive inhibitory synapses as biosensor of released eCB. We found that eCB release is induced through two different pathways. One is dependent on phospholipase Cβ1 (PLCβ1), and triggered by activation of Gq-coupled receptors such as group I metabotropic glutamate receptors and M1/M3 muscarinic receptors. This receptor-driven eCB release is dependent on physiological levels of intracellular Ca2+ concentration ([Ca2+]i), and markedly enhanced by depolarization-induced [Ca2+]i elevation. The other pathway is independent of PLCβ1, and triggered by [Ca2+]i elevation without receptor activation. The [Ca2+]i level required for this pathway is significantly higher than that required for the enhancement of PLCβ1-dependent pathway. The released eCB acts retrogradely onto presynaptic cannabinoid CB1 receptors and suppresses transmitter release. These results indicate that transmitter release is regulated by postsynaptic Gq-coupled receptors and [Ca2+]i through the retrograde eCB signal, and that PLCβ1 serves as a coincidence detector through its Ca2+ dependency for triggering eCB release in hippocampal neurons. [Jpn J Physiol 55 Suppl:S18 (2005)]
