Role of the actomyosin cytoskeleton on the synaptic effects of the type-1 cannabinoid receptor (CB1R)

Des résultats récents de l'équipe d’accueil suggèrent que l'activation du récepteur cannabinoid de type 1 (CB1R) induit une restructuration importante des neurones aux travers du cytosquelette actomyosine. Cette thèse à pour but de poursuivre la caractérisation de ce mécanisme au niveau synaptique. Ceci sera accompli au travers de la dissection pharmacologique des mécanismes moléculaires en aval du récepteur CB1R aux synapses, par video-microscopie conventionelle, ainsi que par microscopie de superresolution STORM.Recently published results from the hosting team suggest that activation of the type-1 cannabinoid receptor (CB1R) induces significant structural remodelling of neurons through modulation of the actomyosin cytoskeleton. This thesis will aim to further characterize the functional consequences of the influence of CB1R activation in the modulation of the actomyosin cytoskeleton, both at the synaptic level. This aim will be accomplished firstly through pharmacological dissection of the molecular pathways linking CB1R modulation of synaptic function to cytoskeletal remodelling, using both conventional time-lapse videomicroscopy of cultured hippocampal neurons, as well as through superresolution imaging of dynamic changes in presynaptic structure under CB1R activation. Results stemming from this project will potentially provide a new molecular pathway underlying well established functions of CB1R as well as providing a novel framework through which to better understand and treat the effects of cannabinoids in the development of such illnesses as schizophrenia