Hardwiring the brain: endocannabinoids shape neuronal connectivity.

P. Berghuis, A. M. Rajnicek, Y. M. Morozov, R. A. Ross, J. Mulder, G. M. Urban, K. Monory, G. Marsicano, M. Matteoli, A. Canty, A. J. Irving, I. Katona, Y. Yanagawa, P. Rakic, B. Lutz, K. Mackie, T. Harkany
Science. 2007-05-25; 316(5828): 1212-1216
DOI: 10.1126/science.1137406

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1. Science. 2007 May 25;316(5828):1212-6.

Hardwiring the brain: endocannabinoids shape neuronal connectivity.

Berghuis P(1), Rajnicek AM, Morozov YM, Ross RA, Mulder J, Urbán GM, Monory K,
Marsicano G, Matteoli M, Canty A, Irving AJ, Katona I, Yanagawa Y, Rakic P, Lutz
B, Mackie K, Harkany T.

Author information:
(1)Division of Molecular Neurobiology, Department of Medical Biochemistry and
Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.

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.

DOI: 10.1126/science.1137406
PMID: 17525344 [Indexed for MEDLINE]

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