Edgar Soria-Gomez, G. Marsicano et al. dans Neuron

Should I stay or should I go? De l’importance des souvenirs aversifs et du système endocannabinoïde

Habenular CB1 Receptors Control the Expression of Aversive Memories
Edgar Soria-Gómez, Arnau Busquets-Garcia, Fei Hu, Amine Mehidi, Astrid Cannich, Liza Roux, Ines Louit, Lucille Alonso, Theresa Wiesner, Francois Georges, Danièle Verrier, Peggy Vincent, Guillaume Ferreira, Minmin Luo, Giovanni Marsicano
Neuron. 2015 Sep 23. pii: S0896-6273(15)00729-1. doi: 10.1016/j.neuron.2015.08.035. [Epub ahead of print]

Edgar Soria-Gomez: Postdoc, since November 2009 in the team of Giovanni Marsicano. Thesis in July 2009 in the “Universidad Nacional Autonoma de Mexico, UNAM »

Should I stay or should I go? De l’importance des souvenirs aversifs et du système endocannabinoïde

We have been all in a situation where we have to decide what to do when faced a dangerous stimulus, “should I stay or should I go?”. As everybody can imagine, such a “simple” decision could determine the fate of an organism. For example, we all know that a fire alarm means danger; if we decide to omit this information our life could be compromised. Similarly, we also avoid food that in the past cause us some sickness. Thus, we are equipped with neurological mechanisms that allow us to behave in the best way depending of the stimulus.

Thus, the expression of aversive emotional memories are key processes for the survival of individuals in their environment. They prepare the organism to effectively avoid potential dangers, and they are accompanied by a number of physiological responses leading to the adoption of behaviors aiming at removing the threat situation. In the brain, aversive memories are under the control of multiple neuronal circuits and molecular mechanisms.
Among them, the brain habenular circuits have been the focus of attention during the last years. On the other hand, the endocannabinoid system (ECS, the target of the main psychoactive component of cannabis) is an important neuromodulator system and has been involved in the regulation of emotional memories.

In the present study, we showed that mice with a genetic deletion of one of the components of the ECS (the CB1 receptor) in habenular circuits present a deficit in the expression of fear conditioning and odor aversion, without affecting neutral or positive memories. Importantly, such deficit is caused by an unbalance of neurotransmission in habenular pathways, involving a specific neurotransmitter, acetylcholine.

Thus, by using different methodological approaches we demonstrated that the ECS exclusively control the expression of aversive (and not neutral or positive) memories independently of the sensory modality by selectively modulating the neurotransmitter acetylcholine (and not glutamate) in habenular circuits.

These results help us understanding how our brain control the expression of aversive memories, and might have interesting consequences for the treatment of diseases linked to these processes, such as anxiety or depression.

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