The endocannabinoid system controls food intake via olfactory processes

Nat Neurosci. 2014 Mar;17(3):407-15. doi: 10.1038/nn.3647. Epub 2014 Feb 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists / pharmacology*
  • Eating / drug effects
  • Eating / physiology*
  • Endocannabinoids / metabolism
  • Endocannabinoids / physiology*
  • Feedback, Physiological / physiology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiology
  • Olfactory Pathways / drug effects
  • Olfactory Pathways / metabolism
  • Olfactory Pathways / physiology*
  • Olfactory Perception / drug effects
  • Olfactory Perception / physiology*
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • CNR1 protein, mouse
  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1