Abstract
Endocannabinoids (eCB) mediate retrograde signal at various brain regions. Postsynaptic release of eCB can suppress neurotransmitter release through activating presynaptic CB1 receptor and cause short-term or long-term synaptic plasticity. The eCB release is induced by strong increase in postsynaptic [Ca2+]i or activation of Gq/11-coupled receptors. Furthermore, coincidence of [Ca2+]i elevation and receptor activation markedly enhances eCB release. Phospholipase C (PLC) is involved in biosynthesis of the major eCB 2-arachidonoylglycerol. To determine the role of PLC in eCB release, we used cultured hippocampal neurons and monitored the eCB release by measuring CB-sensitive synaptic currents. We found that the receptor-driven eCB release was absent in PLCβ1-knockout mice. This PLCβ1-mediated eCB release was dependent on physiological levels of [Ca2+]i. We measured PLCβ1 activity in intact neurons by using exogenous TRPC6 channel as a biosensor for the PLC product diacylglycerol. The receptor-driven TRPC6 currents were absent in PLCβ1-knockout mice and showed a similar [Ca2+]i dependence to that of receptor-driven eCB release. These results indicate that PLCβ1 serves as a coincidence detector for triggering eCB release in the hippocampus. PLCβ contributes to various neuronal signaling. Therefore, Ca2+ dependency of PLCβ may play an important role in various synaptic modulations and plasticity. [J Physiol Sci. 2006;56 Suppl:S31]
