AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training

Nat Neurosci. 2011 Mar;14(3):351-5. doi: 10.1038/nn.2739. Epub 2010 Jan 5.


Two intermingled hypothalamic neuron populations specified by expression of agouti-related peptide (AGRP) or pro-opiomelanocortin (POMC) positively and negatively influence feeding behavior, respectively, possibly by reciprocally regulating downstream melanocortin receptors. However, the sufficiency of these neurons to control behavior and the relationship of their activity to the magnitude and dynamics of feeding are unknown. To measure this, we used channelrhodopsin-2 for cell type-specific photostimulation. Activation of only 800 AGRP neurons in mice evoked voracious feeding within minutes. The behavioral response increased with photoexcitable neuron number, photostimulation frequency and stimulus duration. Conversely, POMC neuron stimulation reduced food intake and body weight, which required melanocortin receptor signaling. However, AGRP neuron-mediated feeding was not dependent on suppressing this melanocortin pathway, indicating that AGRP neurons directly engage feeding circuits. Furthermore, feeding was evoked selectively over drinking without training or prior photostimulus exposure, which suggests that AGRP neurons serve a dedicated role coordinating this complex behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism*
  • Animals
  • Behavior, Animal / physiology
  • Channelrhodopsins
  • Conditioning, Classical / physiology*
  • Eating
  • Feeding Behavior / physiology*
  • Hypothalamus / cytology
  • Hypothalamus / metabolism
  • Melanocortins / metabolism
  • Mice
  • Neurons / metabolism*
  • Photic Stimulation
  • Pro-Opiomelanocortin / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Agouti-Related Protein
  • Channelrhodopsins
  • Melanocortins
  • Recombinant Fusion Proteins
  • Pro-Opiomelanocortin