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Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB₁ cannabinoid receptors (CB₁Rs) are enriched in the axonal growth cones of γ-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoi...

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Published in:	Science (American Association for the Advancement of Science) 2007-05, Vol.316 (5828), p.1212-1216
Main Authors:	Berghuis, Paul, Rajnicek, Ann M, Morozov, Yury M, Ross, Ruth A, Mulder, Jan, Urbán, Gabriella M, Monory, Krisztina, Marsicano, Giovanni, Matteoli, Michela, Canty, Alison, Irving, Andrew J, Katona, István, Yanagawa, Yuchio, Rakic, Pasko, Lutz, Beat, Mackie, Ken, Harkany, Tibor
Format:	Article
Language:	English
Subjects:	Animals Axons Axons - physiology Behavioral neuroscience Biological and medical sciences Brain research Cannabinoid Receptor Modulators - metabolism Cannabinoid Receptor Modulators - physiology Cell Movement Cells, Cultured Cerebral Cortex - cytology Cerebral Cortex - embryology Cerebral Cortex - ultrastructure Development. Senescence. Regeneration. Transplantation Endocannabinoids Fundamental and applied biological sciences. Psychology gamma-Aminobutyric Acid - metabolism Growth cones Growth Cones - diagnostic imaging Growth Cones - physiology Hippocampus In Situ Hybridization Interneurons Interneurons - diagnostic imaging Interneurons - metabolism Interneurons - physiology Medicin och hälsovetenskap Mice Mice, Inbred C57BL Microscopy, Confocal Nervous system Neurites Neurons Pyramidal cells Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - physiology Signal Transduction Steering Stem Cells - metabolism Synapses - diagnostic imaging Synapses - physiology Ultrasonography Vertebrates: nervous system and sense organs Xenopus laevis Xenopus Proteins - physiology
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creator	Berghuis, Paul Rajnicek, Ann M Morozov, Yury M Ross, Ruth A Mulder, Jan Urbán, Gabriella M Monory, Krisztina Marsicano, Giovanni Matteoli, Michela Canty, Alison Irving, Andrew J Katona, István Yanagawa, Yuchio Rakic, Pasko Lutz, Beat Mackie, Ken Harkany, Tibor
description	The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB₁ cannabinoid receptors (CB₁Rs) are enriched in the axonal growth cones of γ-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB₁R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB₁Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.
doi_str_mv	10.1126/science.1137406
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We report that CB₁ cannabinoid receptors (CB₁Rs) are enriched in the axonal growth cones of γ-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB₁R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. 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subjects	Animals Axons Axons - physiology Behavioral neuroscience Biological and medical sciences Brain research Cannabinoid Receptor Modulators - metabolism Cannabinoid Receptor Modulators - physiology Cell Movement Cells, Cultured Cerebral Cortex - cytology Cerebral Cortex - embryology Cerebral Cortex - ultrastructure Development. Senescence. Regeneration. Transplantation Endocannabinoids Fundamental and applied biological sciences. Psychology gamma-Aminobutyric Acid - metabolism Growth cones Growth Cones - diagnostic imaging Growth Cones - physiology Hippocampus In Situ Hybridization Interneurons Interneurons - diagnostic imaging Interneurons - metabolism Interneurons - physiology Medicin och hälsovetenskap Mice Mice, Inbred C57BL Microscopy, Confocal Nervous system Neurites Neurons Pyramidal cells Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - physiology Signal Transduction Steering Stem Cells - metabolism Synapses - diagnostic imaging Synapses - physiology Ultrasonography Vertebrates: nervous system and sense organs Xenopus laevis Xenopus Proteins - physiology
title	Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
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