The team’s previous projects were mainly focused to decipher the closely intertwined relationship between cannabinoid receptor activation and sub-neuronal targeting, by using quantitative in vitro imaging approaches of neurons. In the last years, we became increasingly interested in the understanding of cannabinoid-mediated regulation of neuronal structure. Established techniques range from molecular constructions through imaging-based measurements of GPCR activation in cultured hippocampal neurons to the use of animal models of cerebral plasticity.
Current projects of the team are targeted to develop and use new tools to better understand, at multiple spatio-temporal scales, the role of the highly dynamic actomyosin cytoskeleton in neuronal function and neuropsychiatric pathogenesis.
Cannabinoids contract neurons
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, the major brain target of endocannabinoids and marijuana, 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.
Functional consequences of actomyosin remodelling in the brain
Ultrafast functional Ultrasound (fUS) imaging revealed is adapted to access nervous system function through imaging the neurovascular coupling (Osmanski et al., Nat Commun, 2014; Errico et al., Nature, 2015). An important part of our current efforts is focused to further develop this powerful tool either in collaborative projects or in-house, the latter focused on imaging the functional consequences of actomyosin remodeling on brain structure and connectivity.
5 MAIN PUBLICATIONS
- Várkuti BH, Képiró M, Horváth IÁ, Végner L, Ráti S, Zsigmond Á, Hegyi G, Lenkei Z, Varga M, Málnási-Csizmadia A. A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative. Sci Rep. 2016 May 31;6:26141. doi: 10.1038/srep26141.
- Errico C, Pierre J, Pezet S, Desailly Y, Lenkei Z, Couture O, Tanter M. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature. 2015 Nov 26;527(7579):499-502. doi: 10.1038/nature16066.
- Osmanski BF, Pezet S, Ricobaraza A, Lenkei Z, Tanter M. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution. Nat Commun. 2014 Oct 3;5:5023. doi: 10.1038/ncomms6023.
- Roland AB, Ricobaraza A, Carrel D, Jordan BM, Rico F, Simon A, Humbert-Claude M, Ferrier J, McFadden MH, Scheuring S, Lenkei Z. Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth. Elife. 2014 Sep 15;3:e03159. doi: 10.7554/eLife.03159.
- Thibault K, Carrel D, Bonnard D, Gallatz K, Simon A, Biard M, Pezet S, Palkovits M, Lenkei Z. Activation-dependent subcellular distribution patterns of CB1 cannabinoid receptors in the rat forebrain. Cereb Cortex. 2013 Nov;23(11):2581-91. doi: 10.1093/cercor/bhs240.
