WIKIMEDIA, ALLEN INSTITUTE FOR BRAIN SCIENCEBy increasing odor detection, cannabinoid type-1 (CB1) receptors in the olfactory bulb help mediate feeding behavior in fasted mice, according to a study published in Nature Neuroscience today (February 9). Researchers from the French Institute of Health and Medical Research (INSERM) and elsewhere have uncovered CB1 receptor-dependent mechanisms through which endocannabinoids and exogenous cannabinoids like THC, the active ingredient in marijuana, increase olfaction and subsequent fasting-induced food intake, and suggest that their work points to potential therapeutic targets for feeding behavior-related human diseases like anorexia and obesity.
“The study clearly establishes the relationship of food intake and olfactory processing and implicates the endocannabinoid system as a key player in this signaling pathway,” said Howard University College of Medicine’s Thomas Heinbockel, who has investigated the endocannabinoid system’s functions in the olfactory bulb, but was not involved in the work.
In 2010, INSERM’s Giovanni Marsicano and his colleagues showed that deletion of CB1 from cortical glutamatergic or GABAergic neurons had opposing effects on fasting-induced food intake in mice, implicating the endocannabinoid system in control of feeding behavior. For the present study, the researchers used pharmacological and genetic manipulations as well as an optogenetic approach to investigate connections between sensory input with central processing in the olfactory bulb and subsequent feeding behavior. They found that projections from the cortex to the main olfactory bulb regulate food intake via CB1 receptor signaling by connecting the animal’s feelings of hunger to increased odor processing.
“The olfactory system offers an ideal platform for investigating how the endocannabinoid system modulates a functional neural network to achieve an integrated outcome,” Heinbockel explained in an e-mail. The olfactory bulb receives direct sensory input from the nasal epithelium and the cortex. “This structural organization makes the olfactory bulb . . . significantly different from hippocampus, amygdala, neocortex, and cerebellum to address functional questions of CB1 [receptor] modulation in the brain.”
“This study links cannabinoid drugs to sensory perception—that they definitely do. They hit right on the head,” said biologist Debra Fadool from Florida State University. What’s less clear, however, is whether this connection holds true in non-fasted mice. “And I don’t know [whether it will], because there are studies that show that binding of the CB1 receptor is different when you’re obese,” she continues. “Would all of these pathways occur only with fasting?”
Heinbockel and Fadool agreed that the team has presented substantial experimental evidence to support the CB1 receptor’s role in the hunger-olfaction-food intake circuits proposed. Heinbockel added that while glutamatergic input is not the only centrifugal input to the olfactory bulb, this work marks a significant stride toward understanding an “old question that has not been answered for a long time: How does the smell of a cookie make us want to eat it, and which brain mechanisms allow us to find more food rapidly and reliably when we are hungry?”
E. Soria-Gómez et al., “The endocannabinoid system controls food intake via olfactory processes,” Nature Neuroscience, doi:10.1038/nn.3647, 2014.