Abstract
The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl− current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl− channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca2+ influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl− conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.
| Original language | English |
|---|---|
| Pages (from-to) | 2257-2268 |
| Number of pages | 12 |
| Journal | Pflugers Archiv European Journal of Physiology |
| Volume | 466 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Nov 18 2014 |
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Keywords
- 2-AG
- AEA
- Ca-activated Cl current
- In vitro brain slice preparation
- Whole-cell recording
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)
- Medicine(all)
Cite this
Endocannabinoids produced upon action potential firing evoke a Cl− current via type-2 cannabinoid receptors in the medial prefrontal cortex. / den Boon, Femke S.; Chameau, Pascal; Houthuijs, Kas; Bolijn, Simone; Mastrangelo, Nicolina; Kruse, Chris G.; Maccarrone, Mauro; Wadman, Wytse J.; Werkman, Taco R.
In: Pflugers Archiv European Journal of Physiology, Vol. 466, No. 12, 18.11.2014, p. 2257-2268.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endocannabinoids produced upon action potential firing evoke a Cl− current via type-2 cannabinoid receptors in the medial prefrontal cortex
AU - den Boon, Femke S.
AU - Chameau, Pascal
AU - Houthuijs, Kas
AU - Bolijn, Simone
AU - Mastrangelo, Nicolina
AU - Kruse, Chris G.
AU - Maccarrone, Mauro
AU - Wadman, Wytse J.
AU - Werkman, Taco R.
PY - 2014/11/18
Y1 - 2014/11/18
N2 - The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl− current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl− channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca2+ influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl− conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.
AB - The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl− current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl− channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca2+ influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl− conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.
KW - 2-AG
KW - AEA
KW - Ca-activated Cl current
KW - In vitro brain slice preparation
KW - Whole-cell recording
UR - http://www.scopus.com/inward/record.url?scp=84912026056&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84912026056&partnerID=8YFLogxK
U2 - 10.1007/s00424-014-1502-6
DO - 10.1007/s00424-014-1502-6
M3 - Article
C2 - 24671573
AN - SCOPUS:84912026056
VL - 466
SP - 2257
EP - 2268
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
SN - 0031-6768
IS - 12
ER -