The endocannabinoid system controls food intake via olfactory processes

• Published in: Nature neuroscience Vol. 17; no. 3; pp. 407 - 415
• Main Authors: Soria-Gómez, Edgar, Bellocchio, Luigi, Reguero, Leire, Lepousez, Gabriel, Martin, Claire, Bendahmane, Mounir, Ruehle, Sabine, Remmers, Floor, Desprez, Tifany, Matias, Isabelle, Wiesner, Theresa, Cannich, Astrid, Nissant, Antoine, Wadleigh, Aya, Pape, Hans-Christian, Chiarlone, Anna Paola, Quarta, Carmelo, Verrier, Daniéle, Vincent, Peggy, Massa, Federico, Lutz, Beat, Guzmán, Manuel, Gurden, Hirac, Ferreira, Guillaume, Lledo, Pierre-Marie, Grandes, Pedro, Marsicano, Giovanni
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-03-2014; Nature Publishing Group
• Subjects: 13/44; 14/28; 14/63; 38/1; 38/32; 42/41; 42/44; 42/70; 631/378/1488; 631/378/2624/1703; 64/60; Animal experimentation; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; Cannabinoid Receptor Agonists; Cannabinoid Receptor Agonists - pharmacology; Control; Eating; Eating - drug effects; Eating - physiology; Endocannabinoids; Endocannabinoids - metabolism; Endocannabinoids - physiology; Feedback, Physiological; Feedback, Physiological - physiology; Feeding Behavior; Feeding Behavior - drug effects; Feeding Behavior - physiology; Food; Food and Nutrition; Food consumption; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Neurobiology; Neurosciences; Odors; Olfactory Bulb; Olfactory Bulb - drug effects; Olfactory Bulb - metabolism; Olfactory Bulb - physiology; Olfactory Pathways; Olfactory Pathways - drug effects; Olfactory Pathways - metabolism; Olfactory Pathways - physiology; Olfactory Perception; Olfactory Perception - drug effects; Olfactory Perception - physiology; Physiological aspects; Proteins; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Rhinencephalon; Sensory perception; Synaptic Transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; France; Germany; Paris France; Olfactory bulb; Feeding behaviour
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.3647

This study shows that activation of cannabinoid type-1 (CB1) receptors in the olfactory bulb increases odor detection and food intake in hungry mice. The authors show that this function is mediated by CB1-dependent attenuation of excitatory corticofugal synaptic transmission onto inhibitory granule cells and disinhibition of mitral cells in the main olfactory bulb.
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 (CB
1
) receptors promote food intake in fasted mice by increasing odor detection. CB
1
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 CB
1
receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB
1
receptor–dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.