Hardwiring the brain: endocannabinoids shape neuronal connectivity

Science. 2007 May 25;316(5828):1212-6. doi: 10.1126/science.1137406.

Abstract

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 gamma-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoid Receptor Modulators / physiology*
  • Cell Movement
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / ultrastructure
  • Endocannabinoids*
  • Growth Cones / diagnostic imaging
  • Growth Cones / physiology
  • In Situ Hybridization
  • Interneurons / diagnostic imaging
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / physiology*
  • Signal Transduction
  • Stem Cells / metabolism
  • Synapses / diagnostic imaging
  • Synapses / physiology
  • Ultrasonography
  • Xenopus Proteins / physiology
  • Xenopus laevis
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Xenopus Proteins
  • gamma-Aminobutyric Acid