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Endocannabinoids and Structural Plasticity: Dynamic of the Cannabinoid Type 1 Receptor-induced Signaling and Remodeling at the Single Cell Scale
Alexandre Roland, doctorant. Crédits : ESPCI ParisTechThe cannabinoid type 1 receptor (CB1R) is a among the most highly expressed G protein-coupled receptors in the brain, where it is traditionally recognized as an important presynaptic mediator for retrograde inhibition of neurotransmitter release.
However, the temporal expression pattern and subcellular localization of CB1Rs shows several surprising features. Indeed, CB1R distribution is strongly marked at the axonal membrane, mainly outside the synapses. Furthermore, the CB1R is expressed in the early stages of neuronal development. These data suggest an important extra-synaptic role for CB1Rs. In addition, CB1R displays constitutive activation which responsible for its specific transcytotic targeting to axons.
In this study we particularly focused in the relationship between the activity, targeting and the role of CB1R on neuronal development.
First we found that the CB1R is highly expressed in projection neurons of the developing cortex and gradually translocates in the axonal tracts, suggesting a role in axonal growth.
Then we demonstrated that CB1R activity has a negative effect on the development of dendrites and axons of rat hippocampal neurons in vitro.
Finally, quantitative imaging was performed to measure the constitutive activity of CB1R with sub-neuronal resolution and to identify downstream effectors implicated in CB1R-induced neuronal remodeling.
Our results demonstrate a novel and unexpected feature, rapid contraction of the neuronal actomyosin cortex, as an important putative mechanism for cannabinoid-induced neuronal remodeling.
Key words: cannabinoids, structural plasticity, constitutive activity, cytoskeletton, actomyosin.