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 1 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chang, M. C., Park, J. M., Pelkey, K. A., Grabenstatter, H. L., Xu, D., Linden, D. J., Sutula, T. P., McBain, C. J., & Worley, P. F. (2010). Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nature neuroscience, 13(9), 1090-1097. https://doi.org/10.1038/nn.2621