Cannabinoids regulate an insula circuit controlling water intake

Zhe Zhao, Ana Covelo, Yoni Couderc, Arojit Mitra, Marjorie Varilh, Yifan Wu, Débora Jacky, Rim Fayad, Astrid Cannich, Luigi Bellocchio, Giovanni Marsicano, Anna Beyeler
Current Biology. 2024-05-01; 34(9): 1918-1929.e5
DOI: 10.1016/j.cub.2024.03.053

1. Curr Biol. 2024 May 6;34(9):1918-1929.e5. doi: 10.1016/j.cub.2024.03.053. Epub
2024 Apr 17.

Cannabinoids regulate an insula circuit controlling water intake.

Zhao Z(1), Covelo A(2), Couderc Y(2), Mitra A(2), Varilh M(2), Wu Y(2), Jacky
D(2), Fayad R(2), Cannich A(2), Bellocchio L(2), Marsicano G(3), Beyeler A(4).

Author information:
(1)INSERM 1215, Neurocentre Magendie, University of Bordeaux, 146 rue Léo
Saignat, 33000 Bordeaux, France; Max Planck Florida Institute for Neuroscience,
1 Max Planck Way, Jupiter, FL 33458, USA.
(2)INSERM 1215, Neurocentre Magendie, University of Bordeaux, 146 rue Léo
Saignat, 33000 Bordeaux, France.
(3)INSERM 1215, Neurocentre Magendie, University of Bordeaux, 146 rue Léo
Saignat, 33000 Bordeaux, France. Electronic address:
.
(4)INSERM 1215, Neurocentre Magendie, University of Bordeaux, 146 rue Léo
Saignat, 33000 Bordeaux, France. Electronic address: .

The insular cortex, or insula, is a large brain region involved in the detection
of thirst and the regulation of water intake. However, our understanding of the
topographical, circuit, and molecular mechanisms for controlling water intake
within the insula remains parcellated. We found that type-1 cannabinoid (CB1)
receptors in the insular cortex cells participate in the regulation of water
intake and deconstructed the circuit mechanisms of this control.
Topographically, we revealed that the activity of excitatory neurons in both the
anterior insula (aIC) and posterior insula (pIC) increases in response to water
intake, yet only the specific removal of CB1 receptors in the pIC decreases
water intake. Interestingly, we found that CB1 receptors are highly expressed in
insula projections to the basolateral amygdala (BLA), while undetectable in the
neighboring central part of the amygdala. Thus, we recorded the neurons of the
aIC or pIC targeting the BLA (aIC-BLA and pIC-BLA) and found that they decreased
their activity upon water drinking. Additionally, chemogenetic activation of
pIC-BLA projection neurons decreased water intake. Finally, we uncovered
CB1-dependent short-term synaptic plasticity (depolarization-induced suppression
of excitation [DSE]) selectively in pIC-BLA, compared with aIC-BLA synapses.
Altogether, our results support a model where CB1 receptor signaling promotes
water intake by inhibiting the pIC-BLA pathway, thereby contributing to the fine
top-down control of thirst responses.