The Neuroscience Institute at Bordeaux
The general goal of our group is to understand the cell type-specific role of the endocannabinoid system (ECS) in brain and neuronal functions. The ECS in the brain is formed by the type-1 cannabinoid receptors (CB1), by their endogenous lipid ligands the endocannabinoids (mainly arachidonoyl-ethanolamine, AEA, and 2-arachidonoyl-glycerol, 2-AG), and by the machinery for synthesis and degradation of endocannabinoids. The major effect of CB1 activation is the decrease of neuronal excitability and the presynaptic reduction of neurotransmitter release. As these receptors are expressed both on GABAergic and glutamatergic terminals, their ability to dampen both inhibitory and excitatory neurotransmission could underlie different and even opposite effects of the ECS on neuronal functions and behaviour. To understand the specific role(s) of CB1 signalling in these two neuronal populations, we developed advanced conditional genetic tools, allowing the deletion of CB1 receptors in specific neuronal populations in mice. Using these tools, we studied the effects of the conditional deletion of CB1 in GABAergic and cortical glutamatergic neurons. During the last years, we obtained results pointing to the novel idea that the ECS exerts different functions, depending of the cell type-specific expression of CB1. In detail, CB1 receptors on cortical glutamatergic neurons mediate the well-known neuroprotective and orexigenic functions of the ECS and account for some classical effects of CB1 agonists. Surprisingly, the abundant expression of CB1 in GABAergic neurons is not involved in ECS-dependent neuroprotection and in classical effects of CB1 agonists, but it mediates so-far unsuspected pro-neophobic and anorectic functions of the ECS. These results provided a new vision of the ECS and allowed the publication of interesting articles. They also constitute the ground for our future projects, in which the polymodal mechanisms of action of the ECS will be further detailed and investigated.
Molecular Mechanisms of Behavioral Adaptation