Hardwiring the brain: endocannabinoids shape neuronal connectivity.
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.
Berghuis
Paul
P
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
Rajnicek
Ann M
AM
Morozov
Yury M
YM
Ross
Ruth A
RA
Mulder
Jan
J
Urbán
Gabriella M
GM
Monory
Krisztina
K
Marsicano
Giovanni
G
Matteoli
Michela
M
Canty
Alison
A
Irving
Andrew J
AJ
Katona
István
I
Yanagawa
Yuchio
Y
Rakic
Pasko
P
Lutz
Beat
B
Mackie
Ken
K
Harkany
Tibor
T
D000818:Animals; D001369:Axons / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000648:ultrastructure; D063388:Endocannabinoids; D020439:Growth Cones / Q000000981:diagnostic imaging / Q000502:physiology; D017403:In Situ Hybridization; D007395:Interneurons / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013569:Synapses / Q000000981:diagnostic imaging / Q000502:physiology; D014463:Ultrasonography; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D029867:Xenopus Proteins; D005680:gamma-Aminobutyric Acid