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

Michael C. Chang, Joo Min Park, Kenneth A. Pelkey, Heidi L. Grabenstatter, Desheng Xu, David J Linden, Thomas P. Sutula, Chris J. McBain, Paul F Worley

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1090-1097
Number of pages8
JournalNature Neuroscience
Volume13
Issue number9
DOIs
StatePublished - Sep 2010

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Parvalbumins
Interneurons
Synapses
AMPA Receptors
Neurons
Immediate-Early Genes
Cluster Analysis
Seizures
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. / Chang, Michael C.; Park, Joo Min; Pelkey, Kenneth A.; Grabenstatter, Heidi L.; Xu, Desheng; Linden, David J; Sutula, Thomas P.; McBain, Chris J.; Worley, Paul F.

In: Nature Neuroscience, Vol. 13, No. 9, 09.2010, p. 1090-1097.

Research output: Contribution to journalArticle

Chang, MC, Park, JM, Pelkey, KA, Grabenstatter, HL, Xu, D, Linden, DJ, Sutula, TP, McBain, CJ & Worley, PF 2010, 'Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons', Nature Neuroscience, vol. 13, no. 9, pp. 1090-1097. https://doi.org/10.1038/nn.2621
Chang, Michael C. ; Park, Joo Min ; Pelkey, Kenneth A. ; Grabenstatter, Heidi L. ; Xu, Desheng ; Linden, David J ; Sutula, Thomas P. ; McBain, Chris J. ; Worley, Paul F. / Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. In: Nature Neuroscience. 2010 ; Vol. 13, No. 9. pp. 1090-1097.
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