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This Article Full Text Full Text (PDF) All Versions of this Article: 584/2/407    most recent jphysiol.2007.137505v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohno-Shosaku, T. Articles by Kano, M. Search for Related Content PubMed PubMed Citation Articles by Ohno-Shosaku, T. Articles by Kano, M. Related Collections Neuroscience

¹ Department of Impairment Study, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942, Japan
² Departments of Neurophysiology
³ Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan
⁴ Laboratory of Life Fluctuomatics, Graduate School of Information Sciences, Tohoku University, Sendai 980-8579, Japan

Endocannabinoids are released from neurons in activity-dependent manners, act retrogradely on presynaptic CB₁ cannabinoid receptors, and induce short-term or long-term suppression of transmitter release. The endocannabinoid release is triggered by postsynaptic activation of voltage-gated Ca²⁺ channels and/or G_q-coupled receptors such as group I metabotropic glutamate receptors (I-mGluRs) and M₁/M₃ muscarinic receptors. However, the roles of NMDA receptors, which provide another pathway for Ca²⁺ entry into neurons, in endocannabinoid signalling have been poorly understood. In the present study, we investigated the possible contribution of NMDA receptors in endocannabinoid production by recording IPSCs in cultured hippocampal neurons. Under the conditions minimizing the activation of voltage-gated Ca²⁺ channels, local application of NMDA (200 µM) transiently suppressed cannabinoid-sensitive IPSCs, but not cannabinoid-insensitive IPSCs. This NMDA-induced suppression was abolished by blocking NMDA receptors, CB₁ receptors and diacylglycerol lipase, but not by inhibiting voltage-gated Ca²⁺ channels. When the postsynaptic neuron was dialysed with 30 mM BAPTA, the NMDA-induced suppression was reduced significantly. A lower dose of NMDA (20 µM) exerted little effect when applied alone, but markedly enhanced the cannabinoid-dependent suppression driven by muscarinic receptors or I-mGluRs. These data clearly indicate that the activation of NMDA receptors facilitates the endocannabinoid release either alone or in concert with the G_q-coupled receptors.

(Received 29 May 2007; accepted after revision 3 July 2007; first published online 5 July 2007)
Corresponding author M. Kano: Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan. Email: mkano{at}cns.med.osaka-u.ac.jp

This article has been cited by other articles:

				Y. Hashimotodani, T. Ohno-Shosaku, M. Watanabe, and M. Kano Roles of phospholipase Cbeta and NMDA receptor in activity-dependent endocannabinoid release J. Physiol., October 15, 2007; 584(2): 373 - 380. [Abstract] [Full Text] [PDF]