Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice

Neuron. 2004 Mar 4;41(5):711-22. doi: 10.1016/s0896-6273(04)00074-1.


NPY and alphaMSH are expressed in distinct neurons in the arcuate nucleus of the hypothalamus, where alphaMSH decreases and NPY increases food intake and body weight. Here we use patch-clamp electrophysiology from GFP-labeled POMC and NPY neurons to demonstrate that NPY strongly hyperpolarized POMC neurons through the Y1R-mediated activation of GIRK channels, while the alphaMSH analog, MTII, had no effect on activity of NPY neurons. While initially NPY had similar effects on POMC neurons derived from ob/ob mice, further studies revealed a significant increase in desensitization of the NPY-induced currents in POMC neurons from ob/ob mice. This increase in desensitization was specific to NPY, as GABA(B) and microOR agonists showed unaltered desensitization in POMC neurons from ob/ob mice. These data reveal an intricate and asymmetric interplay between NPY and POMC neurons in the hypothalamus and have important implications for the delineation of the neural circuits that regulate feeding behavior.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / physiology*
  • Baclofen / pharmacology
  • Enkephalin, Methionine / pharmacology
  • In Vitro Techniques
  • Mice
  • Mice, Obese
  • Mice, Transgenic
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptide Y / physiology*
  • Pro-Opiomelanocortin / antagonists & inhibitors*
  • Pro-Opiomelanocortin / physiology


  • Neuropeptide Y
  • Enkephalin, Methionine
  • Pro-Opiomelanocortin
  • Baclofen