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Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex
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 th...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933592/ https://www.ncbi.nlm.nih.gov/pubmed/17684555 http://dx.doi.org/10.1371/journal.pone.0000709 |
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author | Lafourcade, Mathieu Elezgarai, Izaskun Mato, Susana Bakiri, Yamina Grandes, Pedro Manzoni, Olivier J. |
author_facet | Lafourcade, Mathieu Elezgarai, Izaskun Mato, Susana Bakiri, Yamina Grandes, Pedro Manzoni, Olivier J. |
author_sort | Lafourcade, Mathieu |
collection | PubMed |
description | 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 α (DGL-α), 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 Ca(2+) 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. |
format | Text |
id | pubmed-1933592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-19335922007-08-08 Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex Lafourcade, Mathieu Elezgarai, Izaskun Mato, Susana Bakiri, Yamina Grandes, Pedro Manzoni, Olivier J. PLoS One Research Article 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 α (DGL-α), 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 Ca(2+) 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. Public Library of Science 2007-08-08 /pmc/articles/PMC1933592/ /pubmed/17684555 http://dx.doi.org/10.1371/journal.pone.0000709 Text en Lafourcade et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Lafourcade, Mathieu Elezgarai, Izaskun Mato, Susana Bakiri, Yamina Grandes, Pedro Manzoni, Olivier J. Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title_full | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title_fullStr | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title_full_unstemmed | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title_short | Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex |
title_sort | molecular components and functions of the endocannabinoid system in mouse prefrontal cortex |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933592/ https://www.ncbi.nlm.nih.gov/pubmed/17684555 http://dx.doi.org/10.1371/journal.pone.0000709 |
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