The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus

Krisztina Monory; Federico Massa; Michaela Egertová; Matthias Eder; Heike Blaudzun; Ruth Westenbroek; Wolfgang Kelsch; Wolfgang Jacob; Rudolf Marsch; Marc Ekker; Jason Long; John L. Rubenstein; Sandra Goebbels; Klaus-Armin Nave; Matthew During; Matthias Klugmann; Barbara Wölfel; Hans-Ulrich Dodt; Walter Zieglgänsberger; Carsten T. Wotjak; Ken Mackie; Maurice R. Elphick; Giovanni Marsicano; Beat Lutz

doi:10.1016/j.neuron.2006.07.006

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The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus

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The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus

Krisztina Monory, Federico Massa, Michaela Egertová, Matthias Eder, Heike Blaudzun, Ruth Westenbroek, Wolfgang Kelsch, Wolfgang Jacob, Rudolf Marsch, Marc Ekker, …

Neuron (Cambridge, Mass.), Vol.51(4), pp.455-466

17/08/2006

DOI: https://doi.org/10.1016/j.neuron.2006.07.006

PMID: 16908411

Résumé

HUMDISEASE

MOLNEURO

SYSNEURO

Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.

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Titre: The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus
Créateurs - sans rôle: Krisztina Monory - Department of Physiological Chemistry, Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
Federico Massa - Department of Physiological Chemistry, Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
Michaela Egertová - School of Biological and Chemical Sciences, Queen Mary, University of London, E1 4NS London, United Kingdom
Matthias Eder - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Heike Blaudzun - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Ruth Westenbroek - Department of Pharmacology, University of Washington, Seattle, Washington 98195
Wolfgang Kelsch - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Wolfgang Jacob - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Rudolf Marsch - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Marc Ekker - Department of Biology, Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada
Jason Long - Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, California 94143
John L. Rubenstein - Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, California 94143
Sandra Goebbels - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen 37075, Germany
Klaus-Armin Nave - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen 37075, Germany
Matthew During - Department of Molecular Medicine and Pathology, University of Auckland School of Medicine, Auckland 92019, New Zealand
Matthias Klugmann - Department of Molecular Medicine and Pathology, University of Auckland School of Medicine, Auckland 92019, New Zealand
Barbara Wölfel - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Hans-Ulrich Dodt - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Walter Zieglgänsberger - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Carsten T. Wotjak - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany
Ken Mackie - University of Washington
Maurice R. Elphick - School of Biological and Chemical Sciences, Queen Mary, University of London, E1 4NS London, United Kingdom
Giovanni Marsicano - Department of Physiological Chemistry, Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
Beat Lutz - Department of Physiological Chemistry, Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany
Détails de publication: Neuron (Cambridge, Mass.), Vol.51(4), pp.455-466
Éditeur: Elsevier Inc
Nombre de pages: 12
Identifiants: 99160600409311
Unité académique: Institut des Sciences de l'Evolution - Montpellier - ISEM
Langue: English
Type de ressource: Journal article