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Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.


ABSTRACT: The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

SUBMITTER: den Boon FS 

PROVIDER: S-EPMC3295302 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.

den Boon Femke S FS   Chameau Pascal P   Schaafsma-Zhao Qiluan Q   van Aken Willem W   Bari Monica M   Oddi Sergio S   Kruse Chris G CG   Maccarrone Mauro M   Wadman Wytse J WJ   Werkman Taco R TR  

Proceedings of the National Academy of Sciences of the United States of America 20120213 9


The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) c  ...[more]

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