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RESEARCH PRODUCT
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
Michela MatteoliYuchio YanagawaAnn M. RajnicekAndrew J. IrvingKrisztina MonoryBeat LutzKen MackieYury M. MorozovJan MulderPasko RakicAlison J. CantyIstván KatonaGiovanni MarsicanoPaul BerghuisGabriella M. UrbánTibor HarkanyRuth A. Rosssubject
medicine.medical_specialtyCannabinoid receptorGrowth ConesSynaptogenesisXenopus ProteinsBiologyRats Sprague-DawleyMiceXenopus laevisReceptor Cannabinoid CB1ChemorepulsionCell MovementInterneuronsInternal medicineCannabinoid Receptor ModulatorsmedicineAnimalsAxonGrowth coneCells CulturedIn Situ Hybridizationgamma-Aminobutyric AcidUltrasonographyCerebral CortexMicroscopy ConfocalMultidisciplinaryStem Cellsmusculoskeletal neural and ocular physiologyEndocannabinoid systemAxonsRatsMice Inbred C57BLEndocrinologymedicine.anatomical_structurenervous systemSynapsesGABAergiclipids (amino acids peptides and proteins)Axon guidanceNeuroscienceEndocannabinoidsSignal Transductiondescription
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R 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 CB 1 Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-05-25 | Science |