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The endocannabinoid system controls food intake via olfactory processes
Edgar Soria-Gómez, Luigi Bellocchio, Leire Reguero, Gabriel Lepousez, Claire Martin, Mounir Bendahmane, Sabine Ruehle, Floor Remmers, Tifany Desprez, Isabelle Matias, Theresa Wiesner, Astrid Cannich, Antoine Nissant, Aya Wadleigh, Hans-Christian Pape, Anna Paola Chiarlone, Carmelo Quarta, Daniéle Verrier, Peggy Vincent, Federico Massa, Beat Lutz, Manuel Guzmán, Hirac Gurden, Guillaume Ferreira, Pierre-Marie Lledo et al.
Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor–dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.