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

Femke S. Den Boon; Pascal Chameau; Qiluan Schaafsma-Zhao; Willem Van Aken; Monica Bari; Sergio Oddi; Chris G. Kruse; Mauro Maccarrone; Wytse J. Wadman; Taco R. Werkmana

doi:10.1073/pnas.1118167109

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

Femke S. Den Boon, Pascal Chameau, Qiluan Schaafsma-Zhao, Willem Van Aken, Monica Bari, Sergio Oddi, Chris G. Kruse, Mauro Maccarrone, Wytse J. Wadman, Taco R. Werkmana

Fondazione Santa Lucia

Research output: Contribution to journal › Article › peer-review

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 ₂Rs) in the CNS. Here, we show that CB ₂Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP3Rdependent opening of Ca ²⁺-activated Cl- channels. To investigate the functional role of CB ₂R activation, we induced neuronal firing and observed a CB ₂R-mediated reduction in firing frequency. The description of this unique CB ₂R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

Original language	English
Pages (from-to)	3534-3539
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	109
Issue number	9
DOIs	https://doi.org/10.1073/pnas.1118167109
Publication status	Published - Feb 28 2012

Keywords

Calcium-activated chloride current
Firing rate
Intracellular calcium stores
Voltage clamp
Whole-cell current

ASJC Scopus subject areas

General

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10.1073/pnas.1118167109

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Den Boon, F. S., Chameau, P., Schaafsma-Zhao, Q., Van Aken, W., Bari, M., Oddi, S., Kruse, C. G., Maccarrone, M., Wadman, W. J., & Werkmana, T. R. (2012). Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. Proceedings of the National Academy of Sciences of the United States of America, 109(9), 3534-3539. https://doi.org/10.1073/pnas.1118167109

Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. / Den Boon, Femke S.; Chameau, Pascal; Schaafsma-Zhao, Qiluan; Van Aken, Willem; Bari, Monica; Oddi, Sergio; Kruse, Chris G.; Maccarrone, Mauro; Wadman, Wytse J.; Werkmana, Taco R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 9, 28.02.2012, p. 3534-3539.

Research output: Contribution to journal › Article › peer-review

Den Boon, FS, Chameau, P, Schaafsma-Zhao, Q, Van Aken, W, Bari, M, Oddi, S, Kruse, CG, Maccarrone, M, Wadman, WJ & Werkmana, TR 2012, 'Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 9, pp. 3534-3539. https://doi.org/10.1073/pnas.1118167109

Den Boon, Femke S. ; Chameau, Pascal ; Schaafsma-Zhao, Qiluan ; Van Aken, Willem ; Bari, Monica ; Oddi, Sergio ; Kruse, Chris G. ; Maccarrone, Mauro ; Wadman, Wytse J. ; Werkmana, Taco R. / Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 9. pp. 3534-3539.

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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 2Rs) in the CNS. Here, we show that CB 2Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP3Rdependent opening of Ca 2+-activated Cl- channels. To investigate the functional role of CB 2R activation, we induced neuronal firing and observed a CB 2R-mediated reduction in firing frequency. The description of this unique CB 2R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.",

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AU - Van Aken, Willem

AU - Bari, Monica

AU - Oddi, Sergio

AU - Kruse, Chris G.

AU - Maccarrone, Mauro

AU - Wadman, Wytse J.

AU - Werkmana, Taco R.

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AB - 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 2Rs) in the CNS. Here, we show that CB 2Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP3Rdependent opening of Ca 2+-activated Cl- channels. To investigate the functional role of CB 2R activation, we induced neuronal firing and observed a CB 2R-mediated reduction in firing frequency. The description of this unique CB 2R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.

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

Abstract

Keywords

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