The scientific objective of our team is to understand how the expression of the endocannabinoid system (SEC) in various neuronal types regulates differently the implementation of specific brain functions. ESA in the brain includes CB1 receptors, their endogenous lipid ligands, endocannabinoids (mainly arachidonoyl-ethanolamine, AEA, and 2-arachidonoyl-glycerol, 2-AG), and their synthesis and grading machinery.
The major consequence of the activation of CB1 receptors is the decrease in neuronal excitability and the reduction in the pre-synaptic release of the neurotransmitter. Since CB1 receivers are expressed on GABAergic and glutamatergic terminations where they negatively control inhibitory and excitatory transmissions, the location of these receivers could confer different or even opposite functions on the SEC on neuronal activity and behaviour. To understand the specific role of CB1 receptors in each neuronal population (inhibitory or exciting), we have developed advanced genetic tools that have allowed the conditional development of CB1 receptors from specific neuronal populations. Using these tools, we were able to study the consequences of the conditional delegation of CB1 receptors from GABAergic neurons or cortical glutamatergic neurons.
In recent years, we have obtained results that suggest the innovative idea that the SEC performs different functions according to the identity of the neural population in which CB1 receptors are expressed. Thus, CB1 receptors potted by glutamatergic cortical neurons are directly responsible for the classic neuroprotective and orexia functions attributed to the SEC and CB1 receptor agonists. Surprisingly, these functions are independent of the abundant expression of CB1 receptors in GABAergic neurons, the latter being unexpectedly at the origin of pro-ophobic and anorexigenic functions of the SEC.
These results, which provide new insight into the functional role of the SEC, are the basis for interesting publications. They are the cement on which we base our future plans to disseminate this polymodal action of the ESA and its functional impacts.
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