AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

Nat Neurosci. 2012 Jun 24;15(8):1108-10. doi: 10.1038/nn.3147.

Abstract

It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit-impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing-dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors.

Publication types

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

MeSH terms

  • Agouti-Related Protein / physiology*
  • Animals
  • Behavior, Animal / physiology*
  • Cocaine / pharmacology*
  • Dopamine
  • Dopaminergic Neurons / physiology*
  • Female
  • Gene Knockdown Techniques
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Reward

Substances

  • Agouti-Related Protein
  • Agrp protein, mouse
  • Cocaine
  • Dopamine