News & Events

30/09/2020 10h00
Marianne AINCY from Herry's lab will give a presentation entitled 'Long-range projecting prefrontal inhibitory neurons control fear expression'

30/09/2020 10h30
Céline NICOLAS from Beyeler's lab will give a presentation entitled "Role of insular cortex circuits in a model of alcohol use disorder"

Luigi Bellocchio (Marsicano team) and al. in eLife

Cannabis is the most common illicit drug of abuse in the US and globally. In addition, many states in the US, as well as several countries in the world, have legalized the medical and/or recreational use of cannabis. In this rapidly expanding landscape of cannabis use, huge efforts are made to find innovative interventions reducing potential cannabis-evoked harms. Here, we investigated the possible relation between cannabinoids and autophagy, the process of programmed cell “self-digestion”, and asked whether it could be related to the control of motor coordination behavior, one of the best established neurobiological processes impacted by cannabinoids.

We showed that Δ9-tetrahydrocannabinol, the major psychoactive ingredient of cannabis, impairs autophagy and accumulates P62 protein in neurons of the striatum, a brain area that plays a key role in the control of motor coordination. Second, we demonstrate that boosting autophagy, either by pharmacological manipulation (with the FDA-approved mammalian target of rapamycin inhibitor temsirolimus) or by dietary intervention (with the natural, non-toxic disaccharide trehalose), rescues the Δ9-tetrahydrocannabinol-induced impairment of striatal autophagy and motor coordination in mice. Furthermore, we provide evidence that cannabinoid CB1 receptors located on neurons of the striatal direct (stratonigral) pathway, by coupling to mammalian target of rapamycin activation and autophagy inhibition, are indispensable for the motor dyscoordinating activity of Δ9-tetrahydrocannabinol in mice.

Last but not least, using viral mediated genetic manipulation of striatonigral neurons we confirmed that disrupting mammalian target of rapamycin pathway, as well as boosting P62 accumulation in these cells, completely prevents Δ9-tetrahydrocannabinol-induced impairment of striatal autophagy and motor dyscoordination in mice.

Taken together, these findings identify impairment of autophagy as an unprecedented mechanistic link between cannabinoids and motor dyscoordination, and suggest that activators of autophagy might be considered as promising therapeutic tools to treat certain cannabinoid-evoked behavioral alterations.


Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination. Cristina Blázquez, Andrea Ruiz-Calvo, Raquel Bajo-Grañeras, Jérôme M Baufreton, Eva Resel, Marjorie Varilh, Antonio C Pagano Zottola, Yamuna Mariani, Astrid Cannich, José A Rodríguez-Navarro, Giovanni Marsicano, Ismael Galve-Roperh, Luigi Bellocchio, Manuel Guzmán ; eLife 2020;9:e56811 doi: 10.7554/eLife.56811

Andreas Frick (Neurocentre Magendie) has received a Research Award from the Simons Foundation Autism Research Initiative (SFARI).

His project:
Atypical sensory experience is a core feature of Autism Spectrum Disorder (ASD) and may be strongly determinant of other core symptoms of the disorder. Atypical sensory information processing, and associated behavioral symptoms related to the perception of touch, are very common in ASD and exert a strong negative influence on day-to-day life. Nonetheless, there is a surprising paucity of neurobiological studies addressing this aspect of ASD pathology, or specifically attempting to target this symptom for therapeutic rescue. In collaboration with Prof. S. Heinemann (Friedrich-Schiller-University Jena), they are exploring a novel therapeutic strategy for treating sensory symptoms in ASD.