Present address: INSERM U641, Université de la Méditerranée, Faculté de Médecine Secteur-Nord, IFR 11, Marseille, F-13916 France.
The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro
Article first published online: 23 OCT 2008
© The Authors (2008). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 28, Issue 9, pages 1705–1718, November 2008
How to Cite
Vitalis, T., Lainé, J., Simon, A., Roland, A., Leterrier, C. and Lenkei, Z. (2008), The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro. European Journal of Neuroscience, 28: 1705–1718. doi: 10.1111/j.1460-9568.2008.06484.x
- Issue published online: 27 OCT 2008
- Article first published online: 23 OCT 2008
- Received 9 June 2008, revised 28 August 2008, accepted 4 September 2008
- cerebral cortex;
In the rodent and human embryonic brains, the cerebral cortex and hippocampus transiently express high levels of type 1 cannabinoid receptors (CB1Rs), at a developmental stage when these areas are composed mainly of glutamatergic neurons. However, the precise cellular and subcellular localization of CB1R expression as well as effects of CB1R modulation in this cell population remain largely unknown. We report that, starting from embryonic day 12.5, CB1Rs are strongly expressed in both reelin-expressing Cajal-Retzius cells and newly differentiated postmitotic glutamatergic neurons of the mouse telencephalon. CB1R protein is localized first to somato-dendritic endosomes and at later developmental stages it localizes mostly to developing axons. In young axons, CB1Rs are localized both to the axolemma and to large, often multivesicular endosomes. Acute maternal injection of agonist CP-55940 results in the relocation of receptors from axons to somato-dendritic endosomes, indicating the functional competence of embryonic CB1Rs. The adult phenotype of CB1R expression is established around postnatal day 5. By using pharmacological and mutational modulation of CB1R activity in isolated cultured rat hippocampal neurons, we also show that basal activation of CB1R acts as a negative regulatory signal for dendritogenesis, dendritic and axonal outgrowth, and branching. Together, the overall negative regulatory role in neurite development suggests that embryonic CB1R signaling may participate in the correct establishment of neuronal connectivity and suggests a possible mechanism for the development of reported glutamatergic dysfunction in the offspring following maternal cannabis consumption.