Role of the type-1 cannabinoid receptor in the control of water intake
Thesis supervisor: Giovanni MARSICANO PhD

Water intake is crucial for maintaining body fluid homeostasis and animals’ survival. Complex brain processes trigger thirst, which arises upon losing blood volume (i.e. extracellular dehydration) or increasing blood osmolality (i.e. intracellular dehydration), to replenish water for fluid balance. The brain plays a key role in modulating these processes, but the central mechanisms regulating water intake are not fully understood. Type-1 cannabinoid receptors (CB1) are widely and abundantly expressed in the central nervous system where they modulate a variety of functions, such as memory, anxiety and feeding behavior. However, the role of CB1 receptors in the control of water intake is still a matter of debate, since pharmacological activation or blockade of CB1 receptors produced contradictory results in drinking behavior experiments.
My thesis work focuses on the role of CB1 receptors in the control of water intake. By using genetic, pharmacological, anatomical, imaging, and behavioral approaches, I examined the involvement of CB1 receptors in the control of water intake induced by different physiological conditions of extracellular or intracellular dehydration. The results showed that CB1 receptor signaling is required to promote water intake. In particular, global deletion of CB1 receptors does not change plasma osmolality and body water composition, but it decreases water intake induced by water deprivation, systemic or intracerebroventricular (ICV) administration of sodium chloride, or ICV injection of the peptide hormone angiotensin II. In the attempt to better detail the neuronal mechanisms of this function, I discovered that the presence of CB1 receptors in cortical glutamatergic neurons, particularly the ones located in the anterior cingulate cortex (ACC) glutamatergic neurons promote drinking behavior. CB1 receptors are abundantly expressed in axon terminal of ACC glutamatergic neurons projecting to the basolateral amygdala (BLA) and selective expression of CB1 receptors in this circuit is sufficient to guarantee proper drinking behavior in mice. Altogether, these data reveal that CB1 receptors are necessary to promote water intake, and that their presence in the ACC-BLA circuit is sufficient for the top-down control of drinking behavior.
Furthermore, I also provided evidence that CB1 controls water intake in different conditions at other levels, e.g. insular cortex, cholinergic cells, and mitochondria.
In summary, my thesis work analyzed the role of CB1 receptors in distinct cell populations/neuronal circuits for the control of water intake. These results will help further understanding the functions of the ECS and the brain regulation of thirst.

Date de la soutenance: 09/12/2019 - 14h00
Lieu: Centre Broca Nouvelle-Aquitaine Conference Room

mTORC1 and CB1 receptor signaling regulate excitatory glutamatergic inputs onto the hypothalamic paraventricular nucleus in response to energy availability

Wilfrid Mazier, Nicolas Saucisse, Vincent Simon, Astrid Cannich, Giovanni Marsicano, Federico Massa & Daniela Cota

Meeting room: Auditorium Médiathèque Jacques Ellul – Pessac

from Marsicano's lab will give a presentation entitled 'Sport : quand la motivation dépasse la raison'

Recent work has shown that these receptors are also present in the mitochondrial membranes of the brain where they regulate the bioenergetic processes and amnesic effects of cannabinoids. Thus, the pharmacological effects of cannabinoids derived from cannabis are partially dependent on the regulation of cerebral mitochondrial activity.

CB1 receptors in the anterior piriform cortex control odor preference memory
Geoffrey Terral1,2, Arnau Busquets-Garcia1,2, Marjorie Varilh1,2, Svein Achicallende3,4, Astrid Cannich1,2, Luigi Bellocchio1,2, Itziar Bonilla-Del Río3,4, Federico Massa1,2, Nagore Puente3,4, Edgar Soria-Gomez1,2,3,4,5, Pedro Grandes3,4, Guillaume Ferreira2,6,* & Giovanni Marsicano1,2,*

Giovanni Marsicano is member of the prestigious EMBO, European Molecular Biology Organization. The EMBO Election is a recognition of the research excellence and outstanding achievements of a life sciences researcher.

The competition of the SVS doctoral school of the University of Bordeaux has given its verdict: the Neurocentre gleaned 4 of the 16 doctoral contracts. Congratulations to Mohamed-Lyès KACI (Eq. Abrous, Thesis Director Muriel Koehl) who ranks 5th, Emma MESGUICH (Eq. Marsicano, Thesis Director France Chaouloff) who ranks 7th, Pierre-Louis RAUX (Eq. Revest, Thesis Director Monique Vallée) who ranks 11th and Yifan WU (Eq. Beyeler) who ranks 17th. They will join the centre's teams from next school year.