Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons

Nat Neurosci. 2010 Sep;13(9):1090-7. doi: 10.1038/nn.2621. Epub 2010 Aug 22.


Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity and involves both excitatory and inhibitory neurons. The immediate-early gene Narp (neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp-/- mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp-/- mice had increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Extracellular Space / physiology
  • Hippocampus / physiology
  • In Vitro Techniques
  • Interneurons / physiology*
  • Kindling, Neurologic / physiology
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Pathways / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Parvalbumins / metabolism*
  • Presynaptic Terminals / physiology
  • Receptors, AMPA / metabolism
  • Seizures / physiopathology
  • Synapses / physiology*
  • Synaptic Transmission / physiology


  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 4
  • neuronal pentraxin
  • C-Reactive Protein