Roles of phospholipase Cbeta and NMDA receptor in activity-dependent endocannabinoid release.
Endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid receptors and cause various forms of short-term and long-term synaptic plasticity throughout the brain. Using hippocampal and cerebellar neurons, we have revealed that endocannabinoid release can be induced through two different pathways. One is independent of phospholipase Cbeta (PLCbeta) and driven by Ca(2+) elevation alone (Ca(2+)-driven endocannabinoid release, CaER), and the other is PLCbeta-dependent and driven by activation of G(q/11)-coupled receptors (receptor-driven endocannabinoid release, RER). CaER is induced by activation of either voltage-gated Ca(2+) channels or NMDA receptors. RER is functional even at resting Ca(2+) levels (basal RER), but markedly enhanced by a small Ca(2+) elevation (Ca(2+)-assisted RER). In Ca(2+)-assisted RER, PLCbeta serves as a coincidence detector of receptor activation and Ca(2+) elevation. We have also demonstrated that Ca(2+)-assisted RER is essential for the endocannabinoid release triggered by synaptic activity. Our anatomical data show that a set of receptors and enzymes required for RER are well organized so that the excitatory input can trigger RER effectively. Certain forms of spike-timing-dependent plasticity (STDP) are reported to depend on endocannabinoid signalling. The NMDA receptor and PLCbeta might play key roles in the endocannabinoid-dependent forms of STDP as coincidence detectors with different timing dependences.
Hashimotodani
Yuki
Y
Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Ohno-Shosaku
Takako
T
Watanabe
Masahiko
M
Kano
Masanobu
M
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D063388:Endocannabinoids; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D054799:Phospholipase C beta / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology / Q000378:metabolism*; D009435:Synaptic Transmission; D013997:Time Factors
D015220:Calcium Channels; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D016194:Receptors, N-Methyl-D-Aspartate; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium