Top-Down Control of Water Intake by the Endocannabinoid System

Water intake is regulated by neocortical top-down circuits, but their identity and the cellular mechanisms involved are scantly known. Here, we show that endogenous activation of type-1 cannabinoid receptors (CB1) plays a key role in a novel circuit involved in the control of water intake. Endogenous activation of CB1 receptor in cortical glutamatergic neurons, particularly in the anterior cingulate cortex (ACC), promotes water intake. Notably, CB1 receptors are abundantly expressed in glutamatergic axon terminals of the ACC projecting to the basolateral amygdala (BLA) and the selective expression of CB1 receptors in this brain circuit is sufficient to guarantee physiological drinking. Moreover, chemogenetic stimulation of ACC-BLA projecting neurons suppresses drinking behavior, further supporting the role of these neuronal projections on the modulation of water intake. Altogether, these data reveal a new CB1 receptor-dependent cortical circuit involved in the homeostatic control of water intake.