dc.contributor.author | Lafourcade, Mathieu | |
dc.contributor.author | Elezgarai Gabantxo, Izaskun | |
dc.contributor.author | Mato Santos, Susana | |
dc.contributor.author | Bakiri, Yamina | |
dc.contributor.author | Grandes Moreno, Pedro Rolando | |
dc.contributor.author | Manzoni, Olivier J. | |
dc.date.accessioned | 2011-06-02T17:25:17Z | |
dc.date.available | 2011-06-02T17:25:17Z | |
dc.date.issued | 2007-08-08 | |
dc.identifier.citation | PLoS ONE 2(8) : (2007) // e709 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/2718 | |
dc.description | 11 p. | es |
dc.description.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. | es |
dc.description.sponsorship | 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. | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.title | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © 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. | es |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000709 | es |
dc.identifier.doi | 10.1371/journal.pone.0000709 | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | MEDICINE | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |