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

doi:10.1126/science.1137406

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

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447 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 language	English
Pages (from-to)	1212-1216
Number of pages	5
Journal	Science
Volume	316
Issue number	5828
DOIs	https://doi.org/10.1126/science.1137406
Publication status	Published - 25 May 2007

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Berghuis, P., Rajnicek, A. M., Morozov, Y. M., Ross, R. A., Mulder, J., Urban, G. M., Monory, K., Marsicano, G., Matteoli, M., Canty, A., Irving, A. J., Katona, I., Yanagawa, Y., Rakic, P., Lutz, B., Mackie, K., & Harkany, T. (2007). Hardwiring the brain: endocannabinoids shape neuronal connectivity. Science, 316(5828), 1212-1216. https://doi.org/10.1126/science.1137406

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title = "Hardwiring the brain: endocannabinoids shape neuronal connectivity",

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.",

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

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AU - Berghuis, Paul

AU - Rajnicek, Ann M.

AU - Morozov, Yury M.

AU - Ross, Ruth A.

AU - Mulder, Jan

AU - Urban, Gabriella M.

AU - Monory, Krisztina

AU - Marsicano, Giovanni

AU - Matteoli, Michela

AU - Canty, Alison

AU - Irving, Andrew J.

AU - Katona, Istvan

AU - Yanagawa, Yuchio

AU - Rakic, Pasko

AU - Lutz, Beat

AU - Mackie, Ken

AU - Harkany, Tibor

PY - 2007/5/25

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N2 - 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.

AB - 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.

U2 - 10.1126/science.1137406

DO - 10.1126/science.1137406

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SP - 1212

EP - 1216

JO - Science

JF - Science

IS - 5828

ER -

Hardwiring the brain: endocannabinoids shape neuronal connectivity

Abstract

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