Dynamic GABAergic afferent modulation of AgRP neurons

Nat Neurosci. 2016 Dec;19(12):1628-1635. doi: 10.1038/nn.4392. Epub 2016 Sep 19.


Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues before ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the preconsummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor-expressing GABAergic vDMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, leptin receptor-expressing GABAergic vDMH neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / metabolism*
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Feeding Behavior
  • GABAergic Neurons / metabolism*
  • Mice
  • Neuropeptide Y / metabolism
  • Receptors, Leptin / metabolism
  • Sensation / physiology


  • Agouti-Related Protein
  • Neuropeptide Y
  • Receptors, Leptin