Roles of phospholipase Cβ 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 thr...

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Published in:The Journal of physiology 2007-10, Vol.584 (2), p.373-380
Main Authors: Hashimotodani, Yuki, Ohno‐Shosaku, Takako, Watanabe, Masahiko, Kano, Masanobu
Format: Article
Language:English
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Symposium Section Reports: Compartmentalized Signalling In Neurons
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Summary: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 Cβ (PLCβ) and driven by Ca2+ elevation alone (Ca2+‐driven endocannabinoid release, CaER), and the other is PLCβ‐dependent and driven by activation of Gq/11‐coupled receptors (receptor‐driven endocannabinoid release, RER). CaER is induced by activation of either voltage‐gated Ca2+ channels or NMDA receptors. RER is functional even at resting Ca2+ levels (basal RER), but markedly enhanced by a small Ca2+ elevation (Ca2+‐assisted RER). In Ca2+‐assisted RER, PLCβ serves as a coincidence detector of receptor activation and Ca2+ elevation. We have also demonstrated that Ca2+‐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 PLCβ might play key roles in the endocannabinoid‐dependent forms of STDP as coincidence detectors with different timing dependences.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2007.137497