Lafourcade, M;
Elezgarai, I;
Mato, S;
Bakiri, Y;
Grandes, P;
Manzoni, OJ;
(2007)
Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex.
PLOS ONE
, 2
(8)
, Article e709. 10.1371/journal.pone.0000709.
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Abstract
Background. Cannabinoids have deleterious effects on prefrontal cortex (PFC)-mediated functions and multiple evidences link the endogenous cannabinoid (endocannabinoid) system, cannabis use and schizophrenia, a disease in which PFC functions are altered. Nonetheless, the molecular composition and the physiological functions of the endocannabinoid system in the PFC are unknown. Methodology/Principal Findings. Here, using electron microscopy we found that key proteins involved in endocannabinoid signaling are expressed in layers V/VI of the mouse prelimbic area of the PFC: presynaptic cannabinoid CB1 receptors (CB1R) faced postsynaptic mGluR5 while diacylglycerol lipase alpha (DGL-alpha), the enzyme generating the endocannabinoid 2-arachidonoyl-glycerol (2-AG) was expressed in the same dendritic processes as mGluR5. Activation of presynaptic CB1R strongly inhibited evoked excitatory post-synaptic currents. Prolonged synaptic stimulation at 10Hz induced a profound long-term depression (LTD) of layers V/VI excitatory inputs. The endocannabinoid -LTD was presynaptically expressed and depended on the activation of postsynaptic mGluR5, phospholipase C and a rise in postsynaptic Ca2+ as predicted from the localization of the different components of the endocannabinoid system. Blocking the degradation of 2-AG (with URB 602) but not of anandamide (with URB 597) converted subthreshold tetanus to LTD-inducing ones. Moreover, inhibiting the synthesis of 2-AG with Tetrahydrolipstatin, blocked endocannabinoid-mediated LTD. All together, our data show that 2-AG mediates LTD at these synapses. Conclusions/Significance. Our data show that the endocannabinoid -retrograde signaling plays a prominent role in long-term synaptic plasticity at the excitatory synapses of the PFC. Alterations of endocannabinoid -mediated synaptic plasticity may participate to the etiology of PFC-related pathologies.
| Type: | Article |
|---|---|
| Title: | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0000709 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0000709 |
| Language: | English |
| Additional information: | © 2007 Lafourcade et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Work in O.J.M.'s laboratory is supported by grants from INSERM, Région Aquitaine and “ANR 2006 Neurosciences, Neurologie et Psychiatrie n° RPV06092GSA”. P. Grandes' laboratory is supported by MCYT grant BFI2002-01474. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1299379 |
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