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

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)3534-3539
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number9
DOIs
Publication statusPublished - 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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