Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity

P. Berghuis, Ann Marie Rajnicek, Y. M. Morozov, Ruth Alexandra Ross, J. Mulder, G. M. Urban, K. Morony, G. Marsicano, M. Matteoli, A. Canty, A. J. Irving, I. Katona, Y. Yanagawa, P. Rakic, B. Lutz, K. Mackie, T. Harkany

Research output: Contribution to journalArticlepeer-review

422 Citations (Scopus)


The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-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 CB(1)Rs, 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 pages4
Issue number5828
Publication statusPublished - May 2007


  • growth cone guidance
  • rat hippocampus
  • receptor
  • interneurons
  • cannabinoids
  • expression
  • neocortex
  • synapses
  • kinase


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