Varma N, Carlson G C, Ledent C, Alger B E
Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Neurosci. 2001 Dec 15;21(24):RC188. doi: 10.1523/JNEUROSCI.21-24-j0003.2001.
Endocannabinoids are key intercellular signaling molecules in the brain, but the physiological regulation of the endocannabinoid system is not understood. We used the retrograde signal process called depolarization-induced suppression of inhibition (DSI) to study the regulation of this system. DSI is produced when an endocannabinoid released from pyramidal cells suppresses IPSCs by activating CB1R cannabinoid receptors located on inhibitory interneurons. We now report that activation of group I metabotropic glutamate receptors (mGluRs) enhances DSI and that this effect is blocked by antagonists of both mGluRs and of CB1R. We also found that DSI is absent in CB1R knock-out (CB1R(-/-)) mice, and, strikingly, that mGluR agonists have no effect on IPSCs in these mice. We conclude that group I mGluR-induced enhancement of DSI, and suppression of IPSCs, is actually mediated by endocannabinoids. This surprising result opens up new approaches to the investigation of cannabinoid actions in the brain.
内源性大麻素是大脑中关键的细胞间信号分子，但内源性大麻素系统的生理调节机制尚不清楚。我们利用一种名为去极化诱导抑制（DSI）的逆行信号过程来研究该系统的调节。当锥体细胞释放的内源性大麻素通过激活位于抑制性中间神经元上的CB1R大麻素受体来抑制抑制性突触后电流（IPSCs）时，就会产生DSI。我们现在报告，I 型代谢型谷氨酸受体（mGluRs）的激活会增强DSI，并且这种效应会被mGluRs和CB1R的拮抗剂所阻断。我们还发现，在CB1R基因敲除（CB1R(-/-)）小鼠中不存在DSI，而且，令人惊讶的是，mGluR激动剂对这些小鼠的IPSCs没有影响。我们得出结论，I 型mGluR诱导的DSI增强和IPSCs抑制实际上是由内源性大麻素介导的。这一惊人结果为研究大脑中大麻素的作用开辟了新途径。
