Neuropeptide Y activates a G-protein-coupled inwardly rectifying potassium current and dampens excitability in the lateral amygdala

Mol Cell Neurosci. 2008 Nov;39(3):491-8. doi: 10.1016/j.mcn.2008.08.002. Epub 2008 Aug 27.


Neuropeptide Y (NPY) reduces anxiety-related behavior in various animal models. Since activity in the lateral amygdala (LA) seems crucial for fear expression of behavior, we studied the mechanisms of NPY in LA projection neurons using whole-cell patch-clamp recordings in slices of the rat amygdala in vitro. Application of NPY activated a membrane K(+) current with inwardly rectifying properties in 92% of tested neurons. Pharmacological properties were indicative of mediation via Y1 receptors. Nonhydrolyzable analogues of guanine nucleotides and SCH23390 blocked the NPY-activated current. Single-cell RT-PCR demonstrated expression of G-protein-coupled inwardly rectifying K(+) channel (GIRK) subunits GIRK1, GIRK2 and GIRK3, suggesting mediation of the NPY response through GIRK type channels. The NPY-activated current depressed action potential firing in LA projection neurons, through membrane hyperpolarization and decreased input resistance. Functionally, the dampening of excitability in projection neurons of the amygdala may contribute to the decrease in anxiogenic behavior during action of NPY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / anatomy & histology
  • Amygdala / physiology*
  • Animals
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptide Y / metabolism*
  • Patch-Clamp Techniques
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Rats
  • Rats, Long-Evans
  • Receptors, Neuropeptide Y / metabolism


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Neuropeptide Y
  • Protein Subunits
  • Receptors, Neuropeptide Y
  • neuropeptide Y-Y1 receptor