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Séminaire - Zsolt Lenkei Cannabinoid-induced actomyosin contraction shapes neuronal structure and connectivity at multiple spatiotemporal scales

Abstract :

 Zsolt dirige une équipe de recherche à l'ESPCI ( . Il a récemment montré que les récepteurs CB1 étaient impliqués dans la croissance axonale pendant le développement. 

My group worked during the last decade on the mechanism and cell physiological significance of tonic endocannabinoid signaling and its effect on CB1 receptors. After a brief review of this work, I will present new, partly yet unpublished and unexpected findings about the role of presynaptic actomyosin contraction in neuronal structure and synaptic plasticity.

Finally, I will show the interdisciplinary development of new tools to investigate the role of cannabinoid-induced actomyosin contraction in brain structure and connectivity.

My main interest are neuronal G-protein Coupled Receptors or GPCRs. These sensory proteins are important targets of therapeutic and abused drugs, and are usually studied by pharmacology or electrophysiology. Our main model GPCR is the CB1 cannabinoid receptor, one of the most abundant brain GPCRs and the brain target of Δ9-THC, the psychoactive component of marijuana. After having discovered a new axonal targeting model for CB1Rs and having reported the cell-autonomous effects of cannabinoid receptor activation on neurite growth, the team is strongly motivated to investigate the physiological and possible pathophysiological roles of these effects.

We have recently identified the contraction of the neuronal actomyosin cytoskeleton as a mechanism conveying a wide-ranging inhibitory role for cannabinoids in neuronal expansion and growth (Roland et al., eLife, 2014). This mechanism acts downstream of cannabinoid receptor CB1R, atypically coupled to G12/G13 proteins and the Rho-associated kinase ROCK. Such modulation of the neural actomyosin cytoskeleton has not yet been reported downstream of neurotransmitter GPCRs. Therefore our results open previously unexpected perspectives in the study and comprehension of brain function.

Established techniques in the team range from molecular constructions (such as GFP-tagged proteins) through imaging-based measurements of GPCR signaling and traffic in standard cell lines (such as HEK293, CHO), in cultured hippocampal neurons and in utero electroporated organotypic brain slices. We have also validated recently a novel paradigm of functional brain imaging, in collaboration with Dr Mickael Tanter, Institut Langevin, ESPCI-ParisTech. This method, called ultrafast Functional Ultrasound or fUS, through achieving parallel measurement of functional parameters with sensitivity, spatiotemporal resolution and operating simplicity unmatched by current imaging modalities, will open access to previously unexplored aspects of brain function.

Selected publications

Renard et al. Eur Neuropsychopharmacol. 2015
Chatelin et al. Journal of Cerebral Blood Flow and Metabolism, 2015
Errico et al. Nature, 2015
Ladarre et al. Frontiers in Cellular Neuroscience, 2015
Roland et al. eLife, 2014
Osmanski et al. Nature Communications, 2014
Simon et al. J Mol Cell Biol. 2013
Thibault et al. Cerebral Cortex. 2013