Phospholipase Cβ serves as a coincidence detector through its Ca 2+ dependency for triggering retrograde endocannabinoid signal

Yuki Hashimotodani, Takako Ohno-Shosaku, Hiroshi Tsubokawa, Hidenori Ogata, Ken Emoto, Takashi Maejima, Kenji Araishi, Hee Sup Shin, Masanobu Kano

Research output: Contribution to journalArticlepeer-review

246 Citations (Scopus)

Abstract

Endocannabinoids mediate retrograde signal and modulate transmission efficacy at various central synapses. Although endocannabinoid release is induced by either depolarization or activation of Gq/11-coupled receptors, it is markedly enhanced by the coincidence of depolarization and receptor activation. Here we report that this coincidence is detected by phospholipase Cβ1 (PLCβ1) in hippocampal neurons. By measuring cannabinoid-sensitive synaptic currents, we found that the receptor-driven endocannabinoid release was dependent on physiological levels of intracellular Ca2+ concentration ([Ca2+]i), and markedly enhanced by depolarization-induced [Ca2+]i elevation. Furthermore, we measured PLC activity in intact neurons by using exogenous TRPC6 channel as a biosensor for the PLC product diacylglycerol and found that the receptor-driven PLC activation exhibited similar [Ca2+]i dependence to that of endocannabinoid release. Neither endocannabinoid release nor PLC activation was induced by receptor activation in PLCβ1 knockout mice. We therefore conclude that PLCβ1 serves as a coincidence detector through its Ca2+ dependency for endocannabinoid release in hippocampal neurons.

Original languageEnglish
Pages (from-to)257-268
Number of pages12
JournalNeuron
Volume45
Issue number2
DOIs
Publication statusPublished - Jan 20 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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