Hardwiring the brain: endocannabinoids shape neuronal connectivity

Paul Berghuis, Ann M. Rajnicek, Yury M. Morozov, Ruth A. Ross, Jan Mulder, Gabriella M. Urban, Krisztina Monory, Giovanni Marsicano, Michela Matteoli, Alison Canty, Andrew J. Irving, Istvan Katona, Yuchio Yanagawa, Pasko Rakic, Beat Lutz, Ken Mackie, Tibor Harkany

    Research output: Contribution to journalArticlepeer-review

    431 Citations (Scopus)

    Abstract

    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 ?-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.
    Original languageEnglish
    Pages (from-to)1212-1216
    Number of pages5
    JournalScience
    Volume316
    Issue number5828
    DOIs
    Publication statusPublished - 25 May 2007

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